Sam50 Regulates PINK1-Parkin-Mediated Mitophagy by Controlling PINK1 Stability and Mitochondrial Morphology

Publication date: 5 June 2018
Source:Cell Reports, Volume 23, Issue 10
Author(s): Fenglei Jian, Dan Chen, Li Chen, Chaojun Yan, Bin Lu, Yushan Zhu, Shi Chen, Anbing Shi, David C. Chan, Zhiyin Song
PINK1 and Parkin mediate mitophagy, the cellular process that clears dysfunctional mitochondria. Mitophagy is regulated by mitochondrial dynamics, but the molecules linking these two processes remain poorly understood. Here, we show that Sam50, the core component of the sorting and assembly machinery (SAM), is a critical regulator of mitochondrial dynamics and PINK1-Parkin-mediated mitophagy. In response to Sam50 depletion, normal tubular mitochondria are first fragmented and subsequently merged into large spheres. Sam50 interacts with PINK1 to facilitate its processing and degradation. Depletion of Sam50 results in PINK1 accumulation, Parkin recruitment, and mitophagy. Interestingly, Sam50 deficiency induces a piecemeal mode of mitophagy that eliminates mitochondria "bit by bit" but spares mtDNA. In C. elegans, the Sam50 homolog gop-3 is required for the maintenance of mitochondrial morphology and mass. Our findings reveal that Sam50 directly links mitochondrial dynamics and mitophagy and that Sam50 depletion induces elimination of mitochondria without affecting mtDNA content.

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Teaser

The molecular mechanism that mitochondrial dysfunction initiate PINK1-Parkin-mediated mitophagy remain largely unknown. Jian et al. show that Sam50 functions as a critical regulator of mitophagy. Sam50 deficiency stabilizes PINK1 and stimulates PINK1-Parkin-mediated mitophagy by a piecemeal mode. Sam50 depletion induces large spherical mitochondria to protect mtDNA from elimination by mitophagy.


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