Department of Biochemistry and Cell Biology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
Dartmouth Cancer Center, Lebanon, NH, USA.
Autophagy. 2024 Jun;20(6):1447-1448. doi: 10.1080/15548627.2024.2312038. Epub 2024 Mar 6.
Mitophagy is a cellular process that enables the selective degradation of damaged, dysfunctional, or superfluous mitochondria. During mitophagy, specific proteins recognize and tag mitochondria for degradation. These tagged mitochondria are engulfed by specialized structures called phagophores that then mature into autophagosomes/mitophagosomes. Mitophagosomes subsequently transport their mitochondrial cargo to lysosomes, where the mitochondria are broken down and recycled. While the PINK1-PRKN-dependent mitophagy pathway is well understood, mitophagy can also occur independently of this pathway. BNIP3 and BNIP3L/NIX, paralogous membrane proteins on the outer mitochondrial membrane (OMM), serve as ubiquitin-independent mitophagy receptors. Historically, BNIP3 regulation was thought to be primarily transcriptional through HIF1A (hypoxia inducible factor 1 subunit alpha). However, recent work has revealed a significant post-translational dimension, highlighting the strong role of the ubiquitin-proteasome system (UPS) in BNIP3 regulation. With these emerging concepts in mind, we aimed to develop a unified understanding of how steady-state levels of BNIP3 are established and maintained and how this regulation governs underlying cell physiology.
自噬是一种细胞过程，可使受损、功能失调或多余的线粒体选择性降解。在自噬过程中，特定的蛋白质识别并标记要降解的线粒体。这些标记的线粒体被称为吞噬体的专门结构吞噬，然后成熟为自噬体/线粒体自噬体。线粒体自噬体随后将其线粒体货物运输到溶酶体，在线粒体在那里被分解和回收。虽然 PINK1-PRKN 依赖性线粒体自噬途径已经得到很好的理解，但线粒体自噬也可以独立于该途径发生。BNIP3 和 BNIP3L/NIX 是线粒体外膜（OMM）上的同源膜蛋白，作为泛素非依赖性线粒体自噬受体发挥作用。从历史上看，BNIP3 的调节主要是通过 HIF1A（缺氧诱导因子 1 亚基 α）进行转录调节。然而，最近的工作揭示了一个重要的翻译后维度，强调了泛素-蛋白酶体系统（UPS）在 BNIP3 调节中的强大作用。考虑到这些新出现的概念，我们旨在对 BNIP3 的稳态水平是如何建立和维持的以及这种调节如何控制潜在的细胞生理学建立一个统一的理解。
