Hsp90-Cdc37 Chaperone Complex Regulates Ulk1- and Atg13-Mediated Mitophagy
| Autor: | Kristie L. Rose, Der-Fen Suen, Ji Zhang, Mondira Kundu, Do Hyung Kim, Frank C. Dorsey, Chang Hwa Jung, Stephanie M. Prater, Joung Hyuck Joo, Kristin M. Hennessy-Walters, Meredith A. Steeves, Rekha Iyengar, John L. Cleveland, Craig B. Thompson, Kelly McCastlain, Chia Ying Yang, Richard J. Youle, Paul A. Ney, Aashish Joshi |
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| Rok vydání: | 2011 |
| Předmět: |
Atg1
Chaperonins Ubiquitin-Protein Ligases Autophagy-Related Proteins Cell Cycle Proteins Protein Serine-Threonine Kinases Biology Article Cell Line Mice Erythroid Cells Mitophagy Autophagy Animals Autophagy-Related Protein-1 Homolog Humans HSP90 Heat-Shock Proteins Phosphorylation Molecular Biology Adaptor Proteins Signal Transducing Protein Stability Intracellular Signaling Peptides and Proteins Cell Differentiation Cell Biology Autophagy-related protein 13 HSP90-CDC37 chaperone complex Mitochondria Cell biology HEK293 Cells CDC37 Chaperone complex K562 Cells |
| Zdroj: | Molecular Cell. 43(4):572-585 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2011.06.018 |
| Popis: | 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 homologues 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. |
| Databáze: | OpenAIRE |
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