Coordinating BNIP3/NIX-mediated mitophagy in space and time

Mitochondria maintain organellar homeostasis through multiple quality control pathways, including the clearance of defective or unwanted mitochondria by selective autophagy. This removal of mitochondria, mitophagy, is controlled in large part by the outer mitochondrial membrane mitophagy receptors BNIP3 and NIX. While it has long been appreciated that BNIP3 and NIX mediate mitophagy by controlling the recruitment of autophagic machinery to the mitochondrial surface, the requirement for the carefully controlled spatiotemporal regulation of receptor-mediated mitophagy has only recently come to light. Several new factors that regulate the BNIP3/NIX-mediated mitophagy pathway have emerged, and various loss-of-function cell and animal models have revealed the dire consequences of their dysregulation. In this mini-review, we discuss new insights into the mechanisms and roles of the regulation of BNIP3 and NIX and highlight questions that have emerged from the identification of these new regulators.