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

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130 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)572-585
Number of pages14
JournalMolecular Cell
Volume43
Issue number4
DOIs
StatePublished - Aug 19 2011

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    Joo, J. H., Dorsey, F. C., Joshi, A., Hennessy-Walters, K. M., Rose, K. L., McCastlain, K., Zhang, J., Iyengar, R., Jung, C. H., Suen, D. F., Steeves, M. A., Yang, C. Y., Prater, S. M., Kim, D. H., Thompson, C. B., Youle, R. J., Ney, P. A., Cleveland, J. L., & Kundu, M. (2011). Hsp90-Cdc37 Chaperone Complex Regulates Ulk1- and Atg13-Mediated Mitophagy. Molecular Cell, 43(4), 572-585. https://doi.org/10.1016/j.molcel.2011.06.018