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

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.
Mesh Terms:
Animals, Autophagy, Caenorhabditis elegans, Caenorhabditis elegans Proteins, DNA, Mitochondrial, GTP Phosphohydrolases, HEK293 Cells, HeLa Cells, Humans, Membrane Proteins, Mitochondria, Mitochondrial Proteins, Mitophagy, Protein Binding, Protein Kinases, Protein Stability, RNA, Small Interfering, Sequence Homology, Amino Acid, Ubiquitin-Protein Ligases
Cell Rep
Date: Dec. 05, 2017
Download Curated Data For This Publication
221684
Switch View:
  • Interactions 4