Hsp90-Cdc37 Chaperone Complex Regulates Ulk1- and Atg13-Mediated Mitophagy

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• 作者：Joung  ; Hyuck Joo¹ ; ⁷ ; Frank  ; C. Dorsey³ ; ⁷ ; ⁸ ; Aashish Joshi¹ ; ⁷ ; Kristin  ; M. Hennessy-Walters¹ ; ⁷ ; Kristie  ; L. Rose³ ; Kelly McCastlain¹ ; Ji Zhang² ; Rekha Iyengar¹ ; Chang  ; Hwa Jung⁴ ; Der-Fen Suen⁵ ; Meredith  ; A. Steeves³ ; Chia-Ying Yang⁶ ; ⁹ ; Stephanie  ; M. Prater³ ; Do-Hyung Kim⁴ ; Craig  ; B. Thompson⁶ ; ¹⁰ ; Richard  ; J. Youle⁵ ; Paul  ; A. Ney² ; John  ; L. Cleveland³ ; Mondira Kundu¹ ; ^{mondira.kundu@stjude.org"" rel=""nofollow}
• 刊名：Molecular Cell
• 出版年：2011
• 出版时间：19 August 2011
• 年：2011
• 卷：43
• 期：4
• 页码：572-585
• 全文大小：1785 K

文摘

Summary

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.