Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Molecular mechanisms of organelle inheritance: lessons from peroxisomes in yeast

Nature Reviews Molecular Cell Biology volume 11, pages 644–654 (2010)Cite this article

Subjects

Key Points

  • The cytoplasm of eukaryotic cells is elaborately subdivided into membrane-bound compartments called organelles, each precisely tailored for a defined set of biochemical reactions. Cells must maintain their organelle populations to retain the benefits of having organelles.

  • With each division, cells duplicate their organelles and distribute them equitably between the two resultant cells, thus ensuring the faithful transmission of the organelles to future generations.

  • During the past decade, considerable advances have been made towards understanding the molecular mechanisms of organelle inheritance in the budding yeast Saccharomyces cerevisiae. This has facilitated the study of organelle inheritance because the growth of S. cerevisiae is highly polarized, with a mother cell forming a bud that is initially much smaller than itself.

  • Peroxisomes are ubiquitous organelles that contain enzymes responsible for multiple biochemical pathways, notably the β-oxidation of fatty acids and the metabolism of hydrogen peroxide.

  • Peroxisome inheritance in S. cerevisiae is achieved through the directional movement of a subset of peroxisomes to the growing bud, concomitant with the retention of the remaining peroxisomes in the mother cell.

  • Cellular components involved specifically in both peroxisome retention and movement have recently come to light. It is now clear that the regulation of these components is influenced by cell cycle cues and the extent of the peroxisome transfer to the bud, to ultimately achieve a fair and harmonious distribution of these organelles at cell division.

  • One concept that is beginning to emerge is that, even though each organelle uses specific molecular components to ensure its inheritance by future generations, a set of fundamental rules apply to all mechanisms of organelle inheritance.

Abstract

Preserving a functional set of cytoplasmic organelles in a eukaryotic cell requires a process of accurate organelle inheritance at cell division. Studies of peroxisome inheritance in yeast have revealed that polarized transport of a subset of peroxisomes to the emergent daughter cell is balanced by retention mechanisms operating in both mother cell and bud to achieve an equitable distribution of peroxisomes between them. It is becoming apparent that some common mechanistic principles apply to the inheritance of all organelles, but at the same time, inheritance factors specific for each organelle type allow the cell to differentially and specifically control the inheritance of its different organelle populations.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The growth and division cycle of peroxisomes.
Figure 2: Organelle binding to the surface of the Myo2 tail.
Figure 3: Mechanism for Inp2 polarization across the mother cell–bud axis.

Similar content being viewed by others

References

  1. Fagarasanu, A., Fagarasanu, M. & Rachubinski, R. A. Maintaining peroxisome populations: a story of division and inheritance. Annu. Rev. Cell Dev. Biol. 23, 321–344 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Lowe, M. & Barr, F. A. Inheritance and biogenesis of organelles in the secretory pathway. Nature Rev. Mol. Cell Biol. 8, 429–439 (2007).

    Article  CAS  Google Scholar 

  3. Shorter, J. & Warren, G. Golgi architecture and inheritance. Annu. Rev. Cell Dev. Biol. 18, 379–420 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Warren, G. & Wickner, W. Organelle inheritance. Cell 84, 395–400 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Bonifacino, J. S. & Glick, B. S. The mechanisms of vesicle budding and fusion. Cell 116, 153–166 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. Fagarasanu, A. & Rachubinski, R. A. Orchestrating organelle inheritance in Saccharomyces cerevisiae. Curr. Opin. Microbiol. 10, 528–538 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Akhmanova, A. & Hammer, J. A. III. Linking molecular motors to membrane cargo. Curr. Opin. Cell Biol. 22, 479–487 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dunster, K., Toh, B. H. & Sentry, J. W. Early endosomes, late endosomes, and lysosomes display distinct partitioning strategies of inheritance with similarities to Golgi-derived membranes. Eur. J. Cell Biol. 81, 117–124 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Kredel, S. et al. mRuby, a bright monomeric red fluorescent protein for labeling of subcellular structures. PLoS. ONE. 4, e4391 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sheahan, M. B., Rose, R. J. & McCurdy, D. W. Organelle inheritance in plant cell division: the actin cytoskeleton is required for unbiased inheritance of chloroplasts, mitochondria and endoplasmic reticulum in dividing protoplasts. Plant J. 37, 379–390 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Shima, D. T., Cabrera-Poch, N., Pepperkok, R. & Warren, G. An ordered inheritance strategy for the Golgi apparatus: visualization of mitotic disassembly reveals a role for the mitotic spindle. J. Cell Biol. 141, 955–966 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yaffe, M. P., Stuurman, N. & Vale, R. D. Mitochondrial positioning in fission yeast is driven by association with dynamic microtubules and mitotic spindle poles. Proc. Natl Acad. Sci. USA 100, 11424–11428 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pruyne, D. & Bretscher, A. Polarization of cell growth in yeast. I. Establishment and maintenance of polarity states. J. Cell Sci. 113, 365–375 (2000).

    CAS  PubMed  Google Scholar 

  14. Pruyne, D., Legesse-Miller, A., Gao, L., Dong, Y. & Bretscher, A. Mechanisms of polarized growth and organelle segregation in yeast. Annu. Rev. Cell Dev. Biol. 20, 559–591 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Bretscher, A. Polarized growth and organelle segregation in yeast: the tracks, motors, and receptors. J. Cell Biol. 160, 811–816 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Evangelista, M., Pruyne, D., Amberg, D. C., Boone, C. & Bretscher, A. Formins direct Arp2/3-independent actin filament assembly to polarize cell growth in yeast. Nature Cell Biol. 4, 260–269 (2002).

    Article  PubMed  Google Scholar 

  17. Pruyne, D. et al. Role of formins in actin assembly: nucleation and barbed-end association. Science 297, 612–615 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Sagot, I., Rodal, A. A., Moseley, J., Goode, B. L. & Pellman, D. An actin nucleation mechanism mediated by Bni1 and profilin. Nature Cell Biol. 4, 626–631 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. Sagot, I., Klee, S. K. & Pellman, D. Yeast formins regulate cell polarity by controlling the assembly of actin cables. Nature Cell Biol. 4, 42–50 (2002).

    Article  CAS  PubMed  Google Scholar 

  20. Cabib, E., Roh, D. H., Schmidt, M., Crotti, L. B. & Varma, A. The yeast cell wall and septum as paradigms of cell growth and morphogenesis. J. Biol. Chem. 276, 19679–19682 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Pruyne, D., Gao, L., Bi, E. & Bretscher, A. Stable and dynamic axes of polarity use distinct formin isoforms in budding yeast. Mol. Biol. Cell 15, 4971–4989 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Reck-Peterson, S. L., Provance, D. W., Jr, Mooseker, M. S. & Mercer, J. A. Class V myosins. Biochim. Biophys. Acta 1496, 36–51 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Seabra, M. C. & Coudrier, E. Rab GTPases and myosin motors in organelle motility. Traffic 5, 393–399 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Sellers, J. R. & Veigel, C. Walking with myosin, V. Curr. Opin. Cell Biol. 18, 68–73 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Catlett, N. L. & Weisman, L. S. The terminal tail region of a yeast myosin-V mediates its attachment to vacuole membranes and sites of polarized growth. Proc. Natl Acad. Sci. USA 95, 14799–14804 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Estrada, P. et al. Myo4p and She3p are required for cortical ER inheritance in Saccharomyces cerevisiae. J. Cell Biol. 163, 1255–1266 (2003). Shows that Myo4 and She3 power the bud-directed motility of the cortical ER, indicating that cortical ER inheritance is actin-based, in contrast to the microtubule-based inheritance of the perinuclear ER.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Shepard, K. A. et al. Widespread cytoplasmic mRNA transport in yeast: identification of 22 bud-localized transcripts using DNA microarray analysis. Proc. Natl Acad. Sci. USA 100, 11429–11434 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rossanese, O. W. et al. A role for actin, Cdc1p, and Myo2p in the inheritance of late Golgi elements in Saccharomyces cerevisiae. J. Cell Biol. 153, 47–62 (2001). Shows that late Golgi elements are transported to the bud by Myo2 along actin cables and are retained in the bud by Myo2. The authors propose that early Golgi elements do not display bud-directed motility and arise from ER membranes present in the bud.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hill, K. L., Catlett, N. L. & Weisman, L. S. Actin and myosin function in directed vacuole movement during cell division in Saccharomyces cerevisiae. J. Cell Biol. 135, 1535–1549 (1996). Shows that Myo2, guided by actin tracks, is the molecular motor responsible for the transport of the vacuolar segregation structure into the bud.

    Article  CAS  PubMed  Google Scholar 

  30. Ishikawa, K. et al. Identification of an organelle-specific myosin V receptor. J. Cell Biol. 160, 887–897 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tang, F. et al. Regulated degradation of a class V myosin receptor directs movement of the yeast vacuole. Nature 422, 87–92 (2003). References 30 and 31 show that Vac17 is part of the receptor complex that recruits Myo2 to the vacuole and that the abundance of Vac17 fluctuates in the cell cycle in parallel to vacuole motility, suggesting that receptor complex assembly and disassembly helps coordinate organelle positioning with the cell cycle.

    Article  CAS  PubMed  Google Scholar 

  32. Fagarasanu, A., Fagarasanu, M., Eitzen, G. A., Aitchison, J. D. & Rachubinski, R. A. The peroxisomal membrane protein Inp2p is the peroxisome-specific receptor for the myosin V motor Myo2p of Saccharomyces cerevisiae. Dev. Cell 10, 587–600 (2006). Shows that Inp2 is the peroxisomal receptor for Myo2 and has similar cell cycle dynamics to Vac17, suggesting a general mechanism by which cell cycle cues trigger the synthesis and turnover of receptors for molecular motors to coordinate organelle motility and the cell cycle.

    Article  CAS  PubMed  Google Scholar 

  33. Hoepfner, D., van Den Berg, M., Philippsen, P., Tabak, H. F. & Hettema, E. H. A role for Vps1p, actin, and the Myo2p motor in peroxisome abundance and inheritance in Saccharomyces cerevisiae. J. Cell Biol. 155, 979–990 (2001). The first study of peroxisome inheritance in yeast, showing that peroxisome movement is driven by Myo2 along actin cables and that Vps1 has a role in the fission of peroxisomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Altmann, K., Frank, M., Neumann, D., Jakobs, S. & Westermann, B. The class V myosin motor protein, Myo2, plays a major role in mitochondrial motility in Saccharomyces cerevisiae. J. Cell Biol. 181, 119–130 (2008). Implicates Myo2 in the bud-directed motility of mitochondria, thus putting an end to the controversy on the nature of the power generator for mitochondrial movement.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Itoh, T., Toh, E. & Matsui, Y. Mmr1p is a mitochondrial factor for Myo2p-dependent inheritance of mitochondria in the budding yeast. EMBO J. 23, 2520–2530 (2004). The authors identify Mmr1 as a potential Myo2 receptor on the mitochondrial outer membrane.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Govindan, B., Bowser, R. & Novick, P. The role of Myo2, a yeast class V myosin, in vesicular transport. J. Cell Biol. 128, 1055–1068 (1995).

    Article  CAS  PubMed  Google Scholar 

  37. Schott, D., Ho, J., Pruyne, D. & Bretscher, A. The COOH-terminal domain of Myo2p, a yeast myosin V, has a direct role in secretory vesicle targeting. J. Cell Biol. 147, 791–808 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Schott, D. H., Collins, R. N. & Bretscher, A. Secretory vesicle transport velocity in living cells depends on the myosin-V lever arm length. J. Cell Biol. 156, 35–39 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Beach, D. L., Thibodeaux, J., Maddox, P., Yeh, E. & Bloom, K. The role of the proteins Kar9 and Myo2 in orienting the mitotic spindle of budding yeast. Curr. Biol. 10, 1497–1506 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Yin, H., Pruyne, D., Huffaker, T. C. & Bretscher, A. Myosin V orientates the mitotic spindle in yeast. Nature 406, 1013–1015 (2000). References 39 and 40 report an unexpected role for Myo2 in the bud-directed transport of the plus ends of astral microtubules, thus aligning the mitotic spindle with the mother cell–bud axis.

    Article  CAS  PubMed  Google Scholar 

  41. Boldogh, I. R., Ramcharan, S. L., Yang, H. C. & Pon, L. A. A type V myosin (Myo2p) and a Rab-like G-protein (Ypt11p) are required for retention of newly inherited mitochondria in yeast cells during cell division. Mol. Biol. Cell 15, 3994–4002 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Reinke, C. A., Kozik, P. & Glick, B. S. Golgi inheritance in small buds of Saccharomyces cerevisiae is linked to endoplasmic reticulum inheritance. Proc. Natl Acad. Sci. USA 101, 18018–18023 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Fagarasanu, M., Fagarasanu, A., Tam, Y. Y. C., Aitchison, J. D. & Rachubinski, R. A. Inp1p is a peroxisomal membrane protein required for peroxisome inheritance in Saccharomyces cerevisiae. J. Cell Biol. 169, 765–775 (2005). Shows that Inp1 mediates the interaction of peroxisomes with an unidentified cortical structure and that active retention of peroxisomes in the mother cell and bud is crucial for their proper inheritance.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Fagarasanu, M., Fagarasanu, A. & Rachubinski, R. A. Sharing the wealth: peroxisome inheritance in budding yeast. Biochim. Biophys. Acta 1763, 1669–1677 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Pon, L. A. Golgi inheritance: Rab rides the coat-tails. Curr. Biol. 18, R743–R745 (2008).

    Article  CAS  PubMed  Google Scholar 

  46. Purdue, P. E. & Lazarow, P. B. Peroxisome biogenesis. Annu. Rev. Cell Dev. Biol. 17, 701–752 (2001).

    Article  CAS  PubMed  Google Scholar 

  47. Geuze, H. J. et al. Involvement of the endoplasmic reticulum in peroxisome formation. Mol. Biol. Cell 14, 2900–2907 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hoepfner, D., Schildknegt, D., Braakman, I., Philippsen, P. & Tabak, H. F. Contribution of the endoplasmic reticulum to peroxisome formation. Cell 122, 85–95 (2005). Shows that Pex3 targets the general ER after its synthesis and is then sequestered into ER subdomains, from where it buds to reach mature peroxisomes.

    Article  CAS  PubMed  Google Scholar 

  49. Kim, P. K., Mullen, R. T., Schumann, U. & Lippincott-Schwartz, J. The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER. J. Cell Biol. 173, 521–532 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mullen, R. T., Lisenbee, C. S., Miernyk, J. A. & Trelease, R. N. Peroxisomal membrane ascorbate peroxidase is sorted to a membranous network that resembles a subdomain of the endoplasmic reticulum. Plant Cell 11, 2167–2185 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Perry, R. J., Mast, F. D. & Rachubinski, R. A. Endoplasmic reticulum-associated secretory proteins Sec20p, Sec39p, and Dsl1p are involved in peroxisome biogenesis. Eukaryot. Cell 8, 830–843 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tam, Y. Y. C., Fagarasanu, A., Fagarasanu, M. & Rachubinski, R. A. Pex3p initiates the formation of a preperoxisomal compartment from a subdomain of the endoplasmic reticulum in Saccharomyces cerevisiae. J. Biol. Chem. 280, 34933–34939 (2005). Shows that the first 46 amino acids of yeast Pex3 target to a subdomain of the ER. Together with reference 48, this study also shows that peroxisomes can form de novo from ER subdomains.

    Article  CAS  PubMed  Google Scholar 

  53. Titorenko, V. I., Ogrydziak, D. M. & Rachubinski, R. A. Four distinct secretory pathways serve protein secretion, cell surface growth, and peroxisome biogenesis in the yeast Yarrowia lipolytica. Mol. Cell. Biol. 17, 5210–5226 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Titorenko, V. I. & Rachubinski, R. A. The endoplasmic reticulum plays an essential role in peroxisome biogenesis. Trends Biochem. Sci. 23, 231–233 (1998).

    Article  CAS  PubMed  Google Scholar 

  55. van der Zand, A., Braakman, I. & Tabak, H. F. Peroxisomal membrane proteins insert into the endoplasmic reticulum. Mol. Biol. Cell 21, 2057–2065 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Titorenko, V. I. & Mullen, R. T. Peroxisome biogenesis: the peroxisomal endomembrane system and the role of the ER. J. Cell Biol. 174, 11–17 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Mullen, R. T. & Trelease, R. N. The ER-peroxisome connection in plants: development of the “ER semi-autonomous peroxisome maturation and replication” model for plant peroxisome biogenesis. Biochim. Biophys. Acta 1763, 1655–1668 (2006).

    Article  CAS  PubMed  Google Scholar 

  58. Titorenko, V. I. & Rachubinski, R. A. Spatiotemporal dynamics of the ER-derived peroxisomal endomembrane system. Int. Rev. Cell. Mol. Biol. 272, 191–244 (2009).

    Article  CAS  PubMed  Google Scholar 

  59. Schrader, M. & Fahimi, H. D. Growth and division of peroxisomes. Int. Rev. Cytol. 255, 237–290 (2006).

    Article  CAS  PubMed  Google Scholar 

  60. Raychaudhuri, S. & Prinz, W. A. Nonvesicular phospholipid transfer between peroxisomes and the endoplasmic reticulum. Proc. Natl Acad. Sci. USA 105, 15785–15790 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Motley, A. M. & Hettema, E. H. Yeast peroxisomes multiply by growth and division. J. Cell Biol. 178, 399–410 (2007). Shows that peroxisomes do not in general form de novo from the ER in wild-type yeast cells, but multiply by growth and division of pre-existing peroxisomes to maintain their number in a growing cell population.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Schrader, M. & Fahimi, H. D. The peroxisome: still a mysterious organelle. Histochem. Cell Biol. 129, 421–440 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Yan, M., Rayapuram, N. & Subramani, S. The control of peroxisome number and size during division and proliferation. Curr. Opin. Cell Biol. 17, 376–383 (2005).

    Article  CAS  PubMed  Google Scholar 

  64. Munck, J. M., Motley, A. M., Nuttall, J. M. & Hettema, E. H. A dual function for Pex3p in peroxisome formation and inheritance. J. Cell Biol. 187, 463–471 (2009). The authors show that Pex3 acts as the docking factor for Inp1 on the peroxisomal membrane.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ng, S. K., Liu, F., Lai, J., Low, W. & Jedd, G. A tether for Woronin body inheritance is associated with evolutionary variation in organelle positioning. PLoS Genet. 5, e1000521 (2009).

  66. Fagarasanu, A. et al. Myosin-driven peroxisome partitioning in S. cerevisiae. J. Cell Biol. 186, 541–554 (2009). Shows that the levels and distribution of Inp2 are influenced by peroxisome positioning and provides the first evidence for regulatory feedback in adjusting the activity of receptors for molecular motors to achieve effective organelle inheritance.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Pashkova, N., Jin, Y., Ramaswamy, S. & Weisman, L. S. Structural basis for myosin V discrimination between distinct cargoes. EMBO J. 25, 693–700 (2006). Reports the crystal structure of the globular tail of Myo2 at 2.2 Å resolution — the first high-resolution structure of a cargo-binding domain of a molecular motor.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Arai, S., Noda, Y., Kainuma, S., Wada, I. & Yoda, K. Ypt11 functions in bud-directed transport of the Golgi by linking Myo2 to the coatomer subunit Ret2. Curr. Biol. 18, 987–991 (2008).

    Article  CAS  PubMed  Google Scholar 

  69. Lipatova, Z. et al. Direct interaction between a myosin V motor and the Rab GTPases Ypt31/32 is required for polarized secretion. Mol. Biol. Cell 19, 4177–4187 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Miyagishima, S. et al. Microbody proliferation and segregation cycle in the single-microbody alga Cyanidioschyzon merolae. Planta 208, 326–336 (1999).

    Article  CAS  Google Scholar 

  71. Kuravi, K. et al. Dynamin-related proteins Vps1p and Dnm1p control peroxisome abundance in Saccharomyces cerevisiae. J. Cell Sci. 119, 3994–4001 (2006).

    Article  CAS  PubMed  Google Scholar 

  72. Peng, Y. & Weisman, L. S. The cyclin-dependent kinase Cdk1 directly regulates vacuole inheritance. Dev. Cell 15, 478–485 (2008). The first paper to report a role for phosphorylation in Myo2 receptor activity. Vac17 phosphorylation by Cdk1 parallels the cell cycle dynamics of the vacuole, suggesting that Cdk1 acts to control the timing of vacuole movement.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Liakopoulos, D., Kusch, J., Grava, S., Vogel, J. & Barral, Y. Asymmetric loading of Kar9 onto spindle poles and microtubules ensures proper spindle alignment. Cell 112, 561–574 (2003).

    Article  CAS  PubMed  Google Scholar 

  74. Huisman, S. M. et al. Differential contribution of Bud6p and Kar9p to microtubule capture and spindle orientation in S. cerevisiae. J. Cell Biol. 167, 231–244 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Cepeda-Garcia, C. et al. Actin-mediated delivery of astral microtubules instructs Kar9p asymmetric loading to the bud-ward spindle pole. Mol. Biol. Cell 10.1091/mbc.E10-03-0197 (2010). The authors show that the distribution of the Myo2 receptor Kar9 on the plus ends of astral microtubules is influenced by the delivery of these ends to the bud. This paper points to a feedback mechanism based on positioning cues, similar to the one described in reference 66.

  76. Babour, A., Bicknell, A. A., Tourtellotte, J. & Niwa, M. A Surveillance pathway monitors the fitness of the endoplasmic reticulum to control its inheritance. Cell 142, 256–269 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Chang, J. et al. Pex3 peroxisome biogenesis proteins function in peroxisome inheritance as class V myosin receptors. J. Cell Biol. 187, 233–246 (2009). Shows that Pex3 proteins can function as the peroxisomal receptors for class V myosin motors. Together with reference 64, this study implicates the peroxisome biogenic machinery in the process of peroxisome inheritance and the distribution of peroxisomes in cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Weisman, L. S. Organelles on the move: insights from yeast vacuole inheritance. Nature Rev. Mol. Cell Biol. 7, 243–252 (2006).

    Article  CAS  Google Scholar 

  79. Bartholomew, C. R. & Hardy, C. F. p21-activated kinases Cla4 and Ste20 regulate vacuole inheritance in Saccharomyces cerevisiae. Eukaryot. Cell 8, 560–572 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Garcia-Rodriguez, L. J. et al. Mitochondrial inheritance is required for MEN-regulated cytokinesis in budding yeast. Curr. Biol. 19, 1730–1735 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Chung, S. & Takizawa, P. A. Multiple Myo4 motors enhance ASH1 mRNA transport in Saccharomyces cerevisiae. J. Cell Biol. 189, 755–767 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Dunn, B. D., Sakamoto, T., Hong, M. S., Sellers, J. R. & Takizawa, P. A. Myo4p is a monomeric myosin with motility uniquely adapted to transport mRNA. J. Cell Biol. 178, 1193–1206 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Schmid, M., Jaedicke, A., Du, T. G. & Jansen, R. P. Coordination of endoplasmic reticulum and mRNA localization to the yeast bud. Curr. Biol. 16, 1538–1543 (2006).

    Article  CAS  PubMed  Google Scholar 

  84. Hettema, E. H. & Motley, A. M. How peroxisomes multiply. J. Cell Sci. 122, 2331–2336 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Schrader, M. Shared components of mitochondrial and peroxisomal division. Biochim. Biophys. Acta 1763, 531–541 (2006).

    Article  CAS  PubMed  Google Scholar 

  86. Praefcke, G. J. & McMahon, H. T. The dynamin superfamily: universal membrane tubulation and fission molecules? Nature Rev. Mol. Cell Biol. 5, 133–147 (2004).

    Article  CAS  Google Scholar 

  87. Motley, A. M., Ward, G. P. & Hettema, E. H. Dnm1p-dependent peroxisome fission requires Caf4p, Mdv1p and Fis1p. J. Cell Sci. 121, 1633–1640 (2008).

    Article  CAS  PubMed  Google Scholar 

  88. Koch, A., Schneider, G., Luers, G. H. & Schrader, M. Peroxisome elongation and constriction but not fission can occur independently of dynamin-like protein 1. J. Cell Sci. 117, 3995–4006 (2004).

    Article  CAS  PubMed  Google Scholar 

  89. Hoffmann, H. P. & Avers, C. J. Mitochondrion of yeast: ultrastructural evidence for one giant, branched organelle per cell. Science 181, 749–751 (1973).

    Article  CAS  PubMed  Google Scholar 

  90. Koning, A. J., Lum, P. Y., Williams, J. M. & Wright, R. DiOC6 staining reveals organelle structure and dynamics in living yeast cells. Cell. Motil. Cytoskeleton 25, 111–128 (1993).

    Article  CAS  PubMed  Google Scholar 

  91. Yang, H. C., Palazzo, A., Swayne, T. C. & Pon, L. A. A retention mechanism for distribution of mitochondria during cell division in budding yeast. Curr. Biol. 9, 1111–1114 (1999). The first paper to highlight the importance of organelle anchoring in the mother cell for balancing the bud-directed movement of organelles to achieve correct organelle distribution on cell division.

    Article  CAS  PubMed  Google Scholar 

  92. Boldogh, I. R. et al. A protein complex containing Mdm10p, Mdm12p, and Mmm1p links mitochondrial membranes and DNA to the cytoskeleton-based segregation machinery. Mol. Biol. Cell 14, 4618–4627 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hobbs, A. E., Srinivasan, M., McCaffery, J. M. & Jensen, R. E. Mmm1p, a mitochondrial outer membrane protein, is connected to mitochondrial DNA (mtDNA) nucleoids and required for mtDNA stability. J. Cell Biol. 152, 401–410 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Kondo-Okamoto, N., Shaw, J. M. & Okamoto, K. Mmm1p spans both the outer and inner mitochondrial membranes and contains distinct domains for targeting and foci formation. J. Biol. Chem. 278, 48997–49005 (2003).

    Article  CAS  PubMed  Google Scholar 

  95. Burgess, S. M., Delannoy, M. & Jensen, R. E. MMM1 encodes a mitochondrial outer membrane protein essential for establishing and maintaining the structure of yeast mitochondria. J. Cell Biol. 126, 1375–1391 (1994).

    Article  CAS  PubMed  Google Scholar 

  96. Sogo, L. F. & Yaffe, M. P. Regulation of mitochondrial morphology and inheritance by Mdm10p, a protein of the mitochondrial outer membrane. J. Cell Biol. 126, 1361–1373 (1994).

    Article  CAS  PubMed  Google Scholar 

  97. Kornmann, B. et al. An ER-mitochondria tethering complex revealed by a synthetic biology screen. Science 325, 477–481 (2009). The authors use an ingenious genetic screen to identify the Mmm1–Mdm10–Mdm12–Mdm34 complex as a molecular tether between the ER and mitochondria in S. cerevisiae.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Berger, K. H., Sogo, L. F. & Yaffe, M. P. Mdm12p, a component required for mitochondrial inheritance that is conserved between budding and fission yeast. J. Cell Biol. 136, 545–553 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Buvelot, F. S. et al. Bioinformatic and comparative localization of Rab proteins reveals functional insights into the uncharacterized GTPases Ypt10p and Ypt11p. Mol. Cell. Biol. 26, 7299–7317 (2006).

    Article  CAS  Google Scholar 

  100. Itoh, T., Watabe, A., Toh, E. & Matsui, Y. Complex formation with Ypt11p, a Rab-type small GTPase, is essential to facilitate the function of Myo2p, a class V myosin, in mitochondrial distribution in Saccharomyces cerevisiae. Mol. Cell. Biol. 22, 7744–7757 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bertrand, E. et al. Localization of ASH1 mRNA particles in living yeast. Mol. Cell 2, 437–445 (1998).

    Article  CAS  PubMed  Google Scholar 

  102. McCartney, A. W., Greenwood, J. S., Fabian, M. R., White, K. A. & Mullen, R. T. Localization of the tomato bushy stunt virus replication protein p33 reveals a peroxisome-to-endoplasmic reticulum sorting pathway. Plant Cell 17, 3513–3531 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Platta, H. W. & Erdmann, R. Peroxisomal dynamics. Trends Cell Biol. 17, 474–484 (2007).

    Article  CAS  PubMed  Google Scholar 

  104. Huybrechts, S. J. et al. Peroxisome dynamics in cultured mammalian cells. Traffic 10, 1722–1733 (2009).

    Article  CAS  PubMed  Google Scholar 

  105. Nagotu, S., Veenhuis, M. & van der Klei, I. J. Divide et impera: the dictum of peroxisomes. Traffic 11, 175–184 (2010).

    Article  CAS  PubMed  Google Scholar 

  106. Catlett, N. L., Duex, J. E., Tang, F. & Weisman, L. S. Two distinct regions in a yeast myosin-V tail domain are required for the movement of different cargoes. J. Cell Biol. 150, 513–526 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

A.F. is the recipient of a Ralph Steinhauer Award of Distinction from the Government of Alberta. F.D.M. is a Vanier Scholar of the Canadian Institutes of Health Research and the recipient of a Studentship from the Alberta Heritage Foundation for Medical Research. R.A.R. is an International Research Scholar of the Howard Hughes Medical Institute. Research in the Rachubinski laboratory is supported by grants 9208, 15131 and 53326 from the Canadian Institutes of Health Research. The authors thank R. Edwards from the Department of Biochemistry, University of Alberta, for help in rendering the Myo2 structure in figure 2.

Author information

Authors and Affiliations

  1. Department of Cell Biology, University of Alberta, Medical Sciences Building 514, Edmonton, T6G 2H7, Alberta, Canada

    Andrei Fagarasanu, Fred D. Mast, Barbara Knoblach & Richard A. Rachubinski

Authors
  1. Andrei Fagarasanu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fred D. Mast
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Barbara Knoblach
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard A. Rachubinski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard A. Rachubinski.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Richard A. Rachubinski's homepage

Glossary

Formin

One of a group of conserved proteins that nucleate actin assembly by promoting the incorporation of new actin monomers into the growing plus end of an actin filament, with which they remain associated.

Actin monomer

A monomer of actin (also known as globular actin (G-actin)) that polymerizes into helical actin filaments called filamentous actin (F-actin) or microfilaments.

GTPase

A regulatory protein that binds and hydrolyses GTP. GTPases act as molecular switches by alternating between active (usually GTP-bound) and inactive (usually GDP-bound) forms.

COPI vesicle

(Coatomer protein complex I vesicle). A membrane-bound vesicle that buds from Golgi compartments and functions as a carrier in both intra-Golgi transport and Golgi-to-ER retrograde transport.

Actin cable

A long bundle of actin filaments in yeast that can span the entire cell.

Post-Golgi secretory vesicle

A secretory, membrane-bound vesicle that buds from late compartments of the Golgi and is transported along cytoskeletal elements to the plasma membrane.

Cell wall

The rigid, outermost layer of plant cells and some yeasts and bacteria. The yeast cell wall consists almost entirely of homopolysaccharides of glucose, mannose, and N-acetylglucosamine.

Class V myosin

An actin-based molecular motor specialized in the intracellular transport of various cargoes, including membrane-bound organelles.

Cortical endoplasmic reticulum

Tubular–reticular elements of the yeast ER that line the cell periphery.

Late Golgi element

A Golgi structure (or compartment) that is involved in the final stages of protein sorting.

Vacuole

An essential yeast organelle involved in the detoxification, storage and turnover of proteins.

Cytokinesis

The final stage of the cell cycle, when the cytoplasm is divided. In yeast, cytokinesis leads to the separation of mother and daughter cells.

β-oxidation of fatty acids

The process by which a fatty acid in its acyl-CoA-activated form is broken down to generate multiple molecules of acetyl-CoA, which enter the citric acid cycle. In yeast, fatty acid β-oxidation is restricted to peroxisomes.

Pleckstrin homology domain

A sequence ∼100 amino acids in length that binds a special class of lipids called phosphoinositides.

Tail-anchored protein

An integral membrane protein that is post-translationally sorted to organelles, is anchored to the phospholipid bilayer by a single stretch of hydrophobic amino acids close to its C termini and has its N termini exposed to the cytosol.

Woronin body

An organelle that is derived from a peroxisome and is found in filamentous fungi only. Woronin bodies occlude the septal pores between cells in response to wounding, thereby restricting the loss of cytoplasm at sites of injury.

Filamentous fungus

A fungus that grows from its tip by the extension of elongated, thread-like structures called hyphae. Hyphae are usually divided into cellular units by incomplete septa that are perforated with pores large enough to allow organelles to pass through.

Dynamin

One of a group of large GTPases required for the mechanochemical scission of newly formed vesicles in endocytosis, the division of organelles and the regulation of cytokinesis.

Ubiquitin–proteasome system

Essential intracellular machinery for protein degradation, whereby proteins are tagged by the covalent attachment of multiple ubiquitin monomers and then transferred to a large, cytoplasmic, barrel-like protein complex called the proteasome for degradation.

ASH1

(Asymmetric synthesis of HO). A gene encoding a repressor that inhibits the transcription of homothallic switching endonuclease (HO) —an endonuclease that causes mating-type switching in S. cerevisiae. ASH1 mRNA is transported before translation to the bud, where Ash1 prevents the daughter cell from switching its mating type on cell division.

Astral microtubule

(Also called cytoplasmic microtubule). A microtubule that radiates outwards from a centrosome (or spindle body in yeast). Astral microtubules are important for positioning the mitotic spindle during cell division.

Spindle pole body

A multilayered, cylindrical structure embedded in the nuclear envelope that functions as the microtubule-organizing centre in yeast in a manner similar to centrosomes in higher eukaryotes.

Cyclin-dependent kinase

One of a group of Ser/Thr kinases involved in regulating the cell cycle. They are activated by association with a class of proteins called cyclins, the concentration of which varies in a cyclical manner during the cell cycle.

p21-activated kinase

One of a group of evolutionarily conserved Ser/Thr kinases involved in the regulation of actin cytoskeleton dynamics.

Cell cycle checkpoint

A control mechanism that prevents a cell from progressing to the next phase of the cell cycle before the preceding phase has been accurately completed.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fagarasanu, A., Mast, F., Knoblach, B. et al. Molecular mechanisms of organelle inheritance: lessons from peroxisomes in yeast. Nat Rev Mol Cell Biol 11, 644–654 (2010). https://doi.org/10.1038/nrm2960

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2960

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing