Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy Journal Article
| Authors: | Joo, J.; Dorsey, F.; Joshi, A.; Hennessy-Walters, K.; Rose, K.; McCastlain, K.; Zhang, J.; Iyengar, R.; Jung, C.; Suen, D. F.; Steeves, M.; Yang, C. Y.; Prater, S.; Kim, D. H.; Thompson, C.; Youle, R.; Ney, P.; Cleveland, J.; Kundu, M. |
| Article Title: | Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy |
| 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. © 2011 Elsevier Inc. |
| Keywords: | protein phosphorylation; unclassified drug; protein localization; mammalia; animals; cell cycle proteins; mice; cell line; protein stability; protein interaction; cell differentiation; enzyme activation; enzyme activity; protein serine threonine kinase; phosphorylation; regulatory mechanism; protein-serine-threonine kinases; intracellular signaling peptides and proteins; cell damage; adaptor proteins, signal transducing; heat shock protein 90; hsp90 heat-shock proteins; autophagy; mitochondria; protein atg13; ubiquitin-protein ligases; mitochondrion; erythroid cells; chaperone; k562 cells; hek293 cells; cell cycle protein 37; ulk1 enzyme; chaperonins |
| Journal Title: | Molecular Cell |
| Volume: | 43 |
| Issue: | 4 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2011-08-01 |
| Start Page: | 572 |
| End Page: | 585 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2011.06.018 |
| PUBMED: | 21855797 |
| PROVIDER: | scopus |
| PMCID: | PMC3485687 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 6" - "Export Date: 25 June 2012" - "CODEN: MOCEF" - "Source: Scopus" |
