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  • Review Article
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Inositol derivatives: evolution and functions

Nature Reviews Molecular Cell Biology volume 9, pages 151–161 (2008)Cite this article

Key Points

  • Inositols are ancient molecules that were probably first made by a common ancestor of Archaea and Eukarya more than 2,000 million years ago. They are used by relatively few Bacteria.The glycerophosphate backbones of the inositol lipids of Archaea and Eukarya have opposite configurations: sn-glycerol 1-phosphate and 3-phosphate, respectively.

  • Phosphorylated derivatives of PtdIns (PtdInsPns) and inositol polyphosphates (and their pyrophosphorylated derivatives) are only found in — and are ubiquitous in — eukaryotes, suggesting that their origins were a eukaryotic common ancestor.

  • All eukaryotes use PtdInsPns to regulate diverse aspects of membrane trafficking and interaction.The receptor-controlled phosphoinositide-3-kinase and phosphoinositidase C–Ins(1,4,5)P3–Ca2+ signalling pathways appear to have evolved relatively late, in a common ancestor of the 'Metazoa plus Amoebozoa' domain of the eukaryote crown group.

  • Further studies are needed to understand the emerging functions of diverse inositol polyphosphates (and their pyrophosphorylated derivatives).

Abstract

Current research on inositols mainly focuses on myo-inositol (Ins) derivatives in eukaryotic cells, and in particular on the many roles of Ins phospholipids and polyphosphorylated Ins derivatives. However, inositols and their derivatives are more versatile than this — they have acquired diverse functions over the course of evolution. Given the central involvement of primordial bacteria and archaea in the emergence of eukaryotes, what is the status of inositol derivatives in these groups of organisms, and how might inositol, inositol lipids and inositol phosphates have become ubiquitous constituents of eukaryotes? And how, later, might the multifarious functions of inositol derivatives have emerged during eukaryote diversification?

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Figure 1: The diversity and nomenclature of inositols and their derivatives.
Figure 2: Metabolic pathways for the synthesis of inositol derivatives.
Figure 3: Examples of Ins-containing phospholipid structures.
Figure 4: Development of the diverse usage of Ins derivatives through evolution.

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  1. School of Biosciences, University of Birmingham, Birmingham, B15 2TT, UK

    Robert H. Michell

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Glossary

Archaea

The third kingdom of life, distinct from Bacteria and Eukarya. Archaea are unicellular and grow in diverse environments that are often physically extreme. Their DNA replication apparatus is more similar to Eukarya than to Bacteria.

Eukarya

The kingdom of life that is characterized by cells that have nuclei and other membrane-bounded organelles. Eukarya include animals, plants, fungi, amoebozoans and numerous phyla of unicellular organisms.

α-proteobacteria

An ancient bacterial phylogenetic group that includes most phototrophic genera, several genera that metabolize 1-carbon compounds (such as Methylobacterium), plant symbionts (such as Rhizobia) and the Rickettsiaceae (including several pathogens). α-proteobacteria are the ancestors of mitochondria.

Cyanobacteria

Also known as Cyanophyta and blue-green algae. An ancient phylogenetic group of aquatic bacteria that obtain their energy through photosynthesis. Cyanobacteria are the ancestors of chloroplasts.

Actinobacteria

Also known as Actinomycetes. This large group of high G+C Gram-positive bacteria includes pathogenic mycobacteria and soil organisms that decompose organic material. Actinobacteria are sources of commercially valuable secondary metabolites, including antibiotics.

Phospholipid headgroup

The hydrophilic headgroup of a membrane phospholipid that is exposed at the membrane surface.

Halophilic archaea

Archaea that grow only, or preferentially, in high-salt environments.

Archaetidyl

A backbone structure in archaeal glycerophospholipid that comprises glycerol-1-phosphate modified with isoprane-based long-chain ethers on carbons 2 and 3.

Caldarchaetidyl

A double-headed backbone structure in archaeal glycerophospholipids that comprises two glycerol-1-phosphate groups, each of which is modified with isoprane-based long-chain ethers on carbons 2 and 3.

Hyperthermophilic archaea

Archaea that grow only, or preferentially, at very high temperatures (70–100 °C).

Protists

An informal portmanteau term for the many unicellular eukaryotes that are not animals, plants or fungi.

Choanoflagellates

The closest extant relatives of metazoa and fungi. They are free-living (single-cell or colony-forming) eukaryotes that are ubiquitous in aquatic environments, and typically have an ovoid cell body that has a single apical flagellum surrounded by a collar of microvilli.

Microsporidians

Parasitic fungi, some of which are pathogens of metazoa (such as Encephalitozoon cuniculi, the genome of which has been sequenced), that have extremely reduced genomes and mitochondrial remnants (mitosomes).

Glomerular filtrate

The blood plasma filtrate that emerges from the glomerulus of the mammalian kidney, mainly comprising water and low molecular mass solutes (such as ions, sugars and amino acids) that are actively reabsorbed in later segments of the nephron.

Apicomplexans

A large group of spore-forming protists that are characterized by a unique organelle (the apical complex) and are parasites of animals. Apicomplexans cause diseases such as malaria and cryptosporidiosis.

Ecdysozoa

One of the major groups of animals, which includes both the arthropods and nematodes. Many members of this group regularly shed their cuticle by ecdysis, hence the name Ecdysozoa.

Cnidarians

An ancient phylum of marine organisms with rotational symmetry, of which the anthozoa (including sea anemones and corals) were probably the earliest to diverge.

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Michell, R. Inositol derivatives: evolution and functions. Nat Rev Mol Cell Biol 9, 151–161 (2008). https://doi.org/10.1038/nrm2334

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