A role for mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy (557.1)

Abstract

Mitophagy, the autophagic degradation of mitochondria, is an important housekeeping function in eukaryotic cells. Defects in mitophagy occur in degenerative disorders such as Parkinson’s disease, and decreases in the levels of mitophagy correlate with aging phenomena. An important goal is to achieve an understanding of the quality control mechanism(s) that specifically cull defective mitochondrial components or compartments, during mitophagy. Specifically, it is not known whether a small cohort of defective molecules will cause the ablation of an entire compartment, or whether an active process segregates defective molecules from functional ones and allows a more efficient culling mechanism. In this study we have combined a proteomic study with a molecular genetic and cell biology approach to determine whether such a segregation process occurs in yeast mitochondria. We report that different mitochondrial matrix proteins undergo mitophagic degradation at distinctly different rates, supporting the active segregation hypothesis. These differential degradation rates depend on mitochondrial dynamics, suggesting a mechanism that couples a weak physical segregation with mitochondrial fission and fusion to achieve a distillation‐like effect. In agreement with this interpretation, the differential rates of mitophagy that we observed for different mitochondrial matrix proteins strongly correlate with the degree of physical segregation observed for these proteins, within the matrix.Grant Funding Source: Supported by the Israel Science Foundation