Washington University School of Medicine in St. Louis, St. Louis, MO 63110, U.S.A.
University of Texas Southwestern Medical Center, Dallas, TX 75390, U.S.A.
Biochem Soc Trans. 2024 Oct 30;52(5):1969-1979. doi: 10.1042/BST20221364.
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.
线粒体通过多种质量控制途径维持细胞器的稳态，包括通过选择性自噬清除有缺陷或不需要的线粒体。这种线粒体的去除，即线粒体自噬，在很大程度上受到外膜线粒体自噬受体 BNIP3 和 NIX 的控制。虽然人们早就认识到 BNIP3 和 NIX 通过控制自噬机制向线粒体表面的募集来介导线粒体自噬，但受体介导的线粒体自噬的精确时空调节的必要性直到最近才被发现。一些新的调节 BNIP3/NIX 介导的线粒体自噬途径的因子已经出现，各种功能丧失的细胞和动物模型揭示了它们失调的严重后果。在这篇综述中，我们讨论了 BNIP3 和 NIX 调节的机制和作用的新见解，并强调了从这些新调节剂的鉴定中出现的问题。
