Published online Mar 8, 2017. doi: 10.4254/wjh.v9.i7.349
Peer-review started: December 25, 2016
First decision: January 16, 2017
Revised: January 17, 2017
Accepted: February 8, 2017
Article in press: February 13, 2017
Published online: March 8, 2017
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 mitochondria via a 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.
Core tip: A large number of studies have found that the impaired Parkin function or downregulation of expression may induce cancer initiation and progression via mitophagy-related/unrelated mechanisms. Thus, there is a growing belief that Parkin may have tumor suppressor effects. Based on literature and on the authors’ recent publications regarding animal models of alcohol abuse, this paper highlights the various roles of Parkin in the suppression of oncogenesis. Proper understanding of Parkin functions may have therapeutic implications in the treatment of various cancers.