Abstract 148: Parkin Mediates Clearance of Dysfunctional Mitochondria via Multiple Pathways

The ability to clear damaged mitochondria is critical to prevent unnecessary death. Studies have found that dysfunctional mitochondria are rapidly sequestered by autophagosomes and subsequently delivered to lysosomes for degradation. The E3 ubiquitin ligase Parkin has been identified as an important regulator of mitochondrial autophagy. We have previously shown that Parkin plays an important role in clearing dysfunctional mitochondria via autophagy in the heart after myocardial infarction. In this study, we have discovered that Parkin also induces clearance of mitochondria via an autophagy-independent pathway. We found that Parkin mediated clearance of damaged mitochondria in both wild type (WT) and autophagy-deficient Atg5 knockout mouse embryonic fibroblasts (MEFs) treated with the mitochondria uncoupler FCCP. Interestingly, mitochondrial clearance in both cell types was dependent on the presence of Parkin, suggesting that Parkin represents a rate-limiting step. Immunofluorescence analysis revealed that...