Mitophagy, the autophagic degradation of mitochondria, is an important housekeeping function in eukaryotic cells.Defects in mitophagy occur in degenerative disorders such as Parkinsons and Huntingtons diseases, and decreases in the levels of mitophagy correlate with aging phenomena.An important research goal is to understand the quality control mechanism(s) that specifically cull defective mitochondrial components or compartments, during mitophagy.We have combined proteomic studies with a molecular genetic and cell biology approach, to show that different mitochondrial matrix proteins undergo mitophagic degradation at distinctly different rates, and that this correlates with physical segregation of the proteins in the mitochondrial matrix.These differential degradation rates also depend on mitochondrial dynamics, suggesting a mechanism that couples a weak physical segregation with mitochondrial fission and fusion to achieve a distillation-like effect.To further understand these processes, we carried out a phosphoproteomic analysis of mitochondrial proteins under these conditions.We will discuss these results, and their implications for potential mechanism(s) of selectivity and segregation of mitochondrial matrix proteins during mitophagy.