作者: Chengqun Huang , Allen M. Andres , Eric P. Ratliff , Genaro Hernandez , Pamela Lee
DOI: 10.1371/JOURNAL.PONE.0020975
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摘要: Autophagy-dependent mitochondrial turnover in response to cellular stress is necessary for maintaining homeostasis. However, the mechanisms that govern selective targeting of damaged mitochondria are poorly understood. Parkin, an E3 ubiquitin ligase, has been shown be essential clearance mitochondria. Parkin expressed heart, yet its function not investigated context cardioprotection. We previously reported autophagy required cardioprotection by ischemic preconditioning (IPC). In present study, we used simulated ischemia (sI) vitro and IPC hearts investigate role mediating ex vivo vivo. HL-1 cells, sI induced translocation elimination. Langendorff-perfused rat mice subjected regional IPC. Mitochondrial depolarization with uncoupling agent similarly cells hearts. loss was blunted Atg5-deficient revealing requirement Consistent previous reports indicating a p62/SQSTM1 mitophagy, found depletion p62 attenuated mitophagy exacerbated cell death cardiomyocytes sI. While wild type showed increase ubiquitination, knockout exhibited IPC-induced Importantly, ablation abolished cardioprotective effects These results reveal first time crucial