Molecular Cell
Volume 43, Issue 4, 19 August 2011, Pages 572-585
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Article
Hsp90-Cdc37 Chaperone Complex Regulates Ulk1- and Atg13-Mediated Mitophagy

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Summary

Autophagy, the primary recycling pathway of cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the response to cellular stress. The Hsp90-Cdc37 chaperone complex coordinately regulates the activity of select kinases to orchestrate many facets of the stress response. Although both maintain mitochondrial integrity, the relationship between Hsp90-Cdc37 and autophagy has not been well characterized. Ulk1, one of the mammalian homologs of yeast Atg1, is a serine-threonine kinase required for mitophagy. Here we show that the interaction between Ulk1 and Hsp90-Cdc37 stabilizes and activates Ulk1, which in turn is required for the phosphorylation and release of Atg13 from Ulk1, and for the recruitment of Atg13 to damaged mitochondria. Hsp90-Cdc37, Ulk1, and Atg13 phosphorylation are all required for efficient mitochondrial clearance. These findings establish a direct pathway that integrates Ulk1- and Atg13-directed mitophagy with the stress response coordinated by Hsp90 and Cdc37.

Highlights

► Hsp90-Cdc37 interacts with Ulk1, regulating its stability and activation ► Ulk1 phosphorylates Atg13 on S318 and promotes its release to damaged mitochondria ► Ulk1-directed Atg13 S318 phosphorylation is regulated by Hsp90-Cdc37 interactions ► Atg13 S318 phosphorylation is selectively required for mitophagy

Cited by (0)

7

These authors contributed equally to this work

8

Present address: Lilly Research Laboratories, Indianapolis, IN 46037, USA

9

Present address: Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, New York, NY 11790, USA

10

Present address: Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA