Parkin in cancer: Mitophagy-related/unrelated tasks.
Dysfunctional mitochondria may produce excessive reactive oxygen species, thus inducing DNA damage, which may be oncogenic if not repaired. As a major role of the PINK1-Parkin pathway involves selective autophagic clearance of damaged mitochondriaviaa process termed mitophagy, Parkin-mediated mitophagy may be a tumor-suppressive mechanism. As an alternative mechanism for tumor inhibition beyond mitophagy, Parkin has been reported to have other oncosuppressive functions such as DNA repair, negative regulation of cell proliferation and stimulation of p53 tumor suppressor function. The authors recently reported that acute ethanol-induced mitophagy in hepatocytes was associated with Parkin mitochondrial translocation and colocalization with accumulated 8-OHdG (a marker of DNA damage and mutagenicity). This finding suggests: (1) the possibility of Parkin-mediated repair of damaged mitochondrial DNA in hepatocytes of ethanol-treated rats (ETRs) as an oncosuppressive mechanism; and (2) potential induction of cytoprotective mitophagy in ETR hepatocytes if mitochondrial damage is too severe to be repaired. Below is a summary of the various roles Parkin plays in tumor suppression, which may or may not be related to mitophagy. A proper understanding of the various tasks performed by Parkin in tumorigenesis may help in cancer therapy by allowing the PINK1-Parkin pathway to be targeted.
Nabil Eid, Yoichi Kondo, Division of Life Sciences, Department of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Nabil
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Eid
Nabil Eid, Yoichi Kondo, Division of Life Sciences, Department of Anatomy and Cell Biology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Yoichi
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Kondo
8-OHdG; Cancer; Ethanol; Liver; Mitophagy; PINK1; Parkin