2. Academic Validation
  3. Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy

Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy

  • Mol Cell. 2011 Aug 19;43(4):572-85. doi: 10.1016/j.molcel.2011.06.018.
Joung Hyuck Joo 1,  Frank C Dorsey,  Aashish Joshi,  Kristin M Hennessy-Walters,  Kristie L Rose,  Kelly McCastlain,  Ji Zhang,  Rekha Iyengar,  Chang Hwa Jung,  Der-Fen Suen,  Meredith A Steeves,  Chia-Ying Yang,  Stephanie M Prater,  Do-Hyung Kim,  Craig B Thompson,  Richard J Youle,  Paul A Ney,  John L Cleveland,  Mondira Kundu
Affiliations

Affiliation

  • 1 Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
PMID: 21855797 DOI: 10.1016/j.molcel.2011.06.018
Abstract

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.

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