The Role of Autophagy Receptors in Mitophagy

Recent discoveries of autophagic receptors that recognize specific cellular cargo have opened a new chapter in the autophagy field. Selective removal of damaged organelles or protein aggregates is essential for proper cellular homeostasis and survival. Until today, autophagy receptors and their actions have been described in several aspects of selective autophagy including xenophagy, aggrephagy, pexophagy and mitophagy. Receptors have been proven indispensable for the initiation and finalization of specific cargo removal by autophagy. Mitophagy receptors, scAtg32, BNIP3 and BNIP3L/NIX, in LIR-dependent manner, interact with Atg8/LC3/GABARAP family proteins and recruit autophagy machinery to damaged mitochondria. Moreover, it has been shown that BNIP3L/NIX mediates mitochondrial clearance during reticulocyte differentiation. Recent discovery of its homologue BNIP3 enlightened the role of mitophagy receptors in cellular fate, where either survival by mitophagy or death by apoptosis is chosen. Autophagic function of the receptors is regulated by phosphorylation but what the trigger is for the phosphorylation and activation of mitophagy is still obscure. Fine-tuning of mitophagy regulation (and general autophagy) is the major challenge for researchers of our time and their answers will allow us to better understand the role of receptors and autophagy in disease development.