Department of Cell Biology, University of Texas Southwestern Medical Center , Dallas, TX, USA.
Children's Medical Center Research Institute, University of Texas Southwestern Medical Center , Dallas, TX, USA.
J Cell Biol. 2023 Apr 3;222(4). doi: 10.1083/jcb.202204021. Epub 2023 Feb 16.
Mitochondria play critical roles in cellular metabolism and to maintain their integrity, they are regulated by several quality control pathways, including mitophagy. During BNIP3/BNIP3L-dependent receptor-mediated mitophagy, mitochondria are selectively targeted for degradation by the direct recruitment of the autophagy protein LC3. BNIP3 and/or BNIP3L are upregulated situationally, for example during hypoxia and developmentally during erythrocyte maturation. However, it is not well understood how they are spatially regulated within the mitochondrial network to locally trigger mitophagy. Here, we find that the poorly characterized mitochondrial protein TMEM11 forms a complex with BNIP3 and BNIP3L and co-enriches at sites of mitophagosome formation. We find that mitophagy is hyper-active in the absence of TMEM11 during both normoxia and hypoxia-mimetic conditions due to an increase in BNIP3/BNIP3L mitophagy sites, supporting a model that TMEM11 spatially restricts mitophagosome formation.
线粒体在细胞代谢中发挥着关键作用，为了维持其完整性，它们受到几种质量控制途径的调节，包括线粒体自噬。在 BNIP3/BNIP3L 依赖性受体介导的线粒体自噬中，线粒体通过自噬蛋白 LC3 的直接募集被选择性靶向降解。BNIP3 和/或 BNIP3L 在特定情况下上调，例如在缺氧和红细胞成熟过程中发育。然而，它们如何在线粒体网络内进行空间调节以局部引发线粒体自噬尚不清楚。在这里，我们发现，特征不明显的线粒体蛋白 TMEM11 与 BNIP3 和 BNIP3L 形成复合物，并在噬线粒体形成部位富集。我们发现，由于 BNIP3/BNIP3L 线粒体自噬部位的增加，在常氧和缺氧模拟条件下，TMEM11 缺失时线粒体自噬过度活跃，支持 TMEM11 空间限制噬线粒体形成的模型。
