Regulation of PRKN-independent mitophagy.

ABSTRACT

Mitochondria are dynamic, multifunctional cellular organelles that play a fundamental role in maintaining cellular homeostasis. Keeping the quality of mitochondria in check is of essential importance for functioning and survival of the cells. Selective autophagic clearance of flawed mitochondria, a process termed mitophagy, is one of the most prominent mechanisms through which cells maintain a healthy mitochondrial pool. The best-studied pathway through which mitophagy is exerted is the PINK1-PRKN pathway. However, an increasing number of studies have shown an existence of alternative pathways, where different proteins and lipids are able to recruit autophagic machinery independently of PINK1 and PRKN. The significance of PRKN-independent mitophagy pathways is reflected in various physiological and pathophysiological processes, but many questions regarding the regulation and the interplay between these pathways remain open. Here we review the current knowledge and recent progress made in the field of PRKN-independent mitophagy. Particularly we focus on the regulation of various receptors that participate in targeting impaired mitochondria to autophagosomes independently of PRKN.Abbreviations AMPK AMP-activated protein kinase; ATP adenosine triphosphate; BCL2 BCL2 apoptosis regulator; BH BCL2 homology; CCCP Carbonyl cyanide m-chlorophenylhydrazone; CL cardiolipin; ER endoplasmic reticulum; FCCP carbonyl cyanide p-trifluoromethoxyphenylhydrazone; IMM inner mitochondrial membrane; IMS mitochondrial intermembrane space; LIR LC3-interacting region; MDVs mitochondrial-derived vesicles; MTORC1 mechanistic target of rapamycin kinase complex 1; OMM outer mitochondrial membrane; OXPHOS oxidative phosphorylation; PD Parkinson disease; PtdIns3K phosphatidylinositol 3-kinase; RGC retinal ganglion cell; RING really interesting new gene; ROS reactive oxygen species; SUMO small ubiquitin like modifier; TBI traumatic brain injury; TM transmembrane.