JOURNAL ARTICLE

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

Joung Hyuck Joo, 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
Molecular Cell 2011 August 19, 43 (4): 572-85
21855797
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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