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

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Autophagy, Autophagy-Related Protein-1 Homolog, Autophagy-Related Proteins, Cell Cycle Proteins, Cell Differentiation, Cell Line, Chaperonins, Erythroid Cells, HEK293 Cells, HSP90 Heat-Shock Proteins, Humans, Intracellular Signaling Peptides and Proteins, K562 Cells, Mice, Mitochondria, Phosphorylation, Protein Stability, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases
Mol. Cell
Date: Aug. 19, 2011
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