Most cellular stress responses converge on the mitochondria. Consequently, the mitochondria must rapidly respond to maintain cellular homeostasis and physiological demands by fine-tuning a plethora of mitochondria-associated processes. The outer mitochondrial membrane (OMM) proteins are central to mediating mitochondrial dynamics, coupled with continuous fission and fusion. These OMM proteins also have vital roles in controlling mitochondrial quality and serving as mitophagic receptors for autophagosome enclosure during mitophagy. Mitochondrial fission segregates impaired mitochondria in smaller sizes from the mother mitochondria and may favor mitophagy for eliminating damaged mitochondria. Conversely, mitochondrial fusion mixes dysfunctional mitochondria with healthy ones to repair the damage by diluting the impaired components and consequently prevents mitochondrial clearance via mitophagy. Despite extensive research efforts into deciphering the interplay between fission–fusion and mitophagy, it is still not clear whether mitochondrial fission essentially precedes mitophagy. In this review, we summarize recent breakthroughs concerning OMM research, and dissect the functions of these proteins in mitophagy from their traditional roles in fission–fusion dynamics, in response to distinct context, at the intersection of the OMM platform. These insights into the OMM proteins in mechanistic researches would lead to new aspects of mitochondrial quality control and better understanding of mitochondrial homeostasis intimately tied to pathological impacts.

大多数细胞应激反应集中在线粒体上。因此，线粒体必须通过微调过多的线粒体相关过程来快速响应以维持细胞稳态和生理需求。线粒体外膜 (OMM) 蛋白是介导线粒体动力学以及连续裂变和融合的核心。这些 OMM 蛋白在控制线粒体质量和作为线粒体自噬过程中封闭自噬体的线粒体受体方面也具有重要作用。线粒体裂变将受损线粒体与母线粒体分离，尺寸较小，可能有利于线粒体自噬以消除受损线粒体。反过来，线粒体融合将功能失调的线粒体与健康线粒体混合，通过稀释受损成分来修复损伤，从而防止通过线粒体自噬清除线粒体。尽管为破译裂变-融合和线粒体自噬之间的相互作用进行了大量研究，但仍不清楚线粒体裂变是否本质上先于线粒体自噬。在这篇综述中，我们总结了关于 OMM 研究的最新突破，并在 OMM 平台的交叉点上剖析了这些蛋白质在裂变-融合动力学中的传统角色在线粒体自噬中的功能，以响应不同的背景。