Mitochondria are essential organelles for providing energy and metabolic intermediates. In addition, mitochondria are the main sites for reactive oxygen species (ROS) generation and play central roles in cell death. Mitophagy is a critical mechanism for bulk degradation of mitochondria through a process using macroautophagy machinery, and mitophagy mechanism holds a central role in mitochondrial quality control by recognizing damages to the mitochondria and selectively removing the damaged mitochondria. In this process, entire mitochondria are enclosed in a double-membrane vesicle, autophagosome, and delivered to lysosomes for hydrolytic degradation. Upon activation of mitophagy, Parkin ubiquitinates PARIS and promotes its degradation, thereby increasing transcription of PGC-1α and promoting mitochondrial biosynthesis. Dysregulation of mitochondrial function and accumulation of mitochondrial DNA mutations have frequently been observed in human cancers,  the close relationship between mitophagy and cancer is evident through the regulation of expression of Parkin, BNIP3, NIX, and others by representative tumor suppressors such as p53 and Rb and oncogenes such as NF-κB, FOXO3, and HIF-1α. Parkin may act as a tumor suppressor. The expression of another important mitophagy regulator, PINK1, has been reported to be linked to the survival and prognosis of the adrenocortical tumor (ACT). Mitophagy plays a critical role to suppress cancer development. The increase of ROS could be responsible for facilitating cancer development upon mitophagy reduction.


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