Year: 2026
Type: article
Abstract: Mitophagy maintains mitochondrial homeostasis through the selective degradation of damaged or excess mitochondria. Recently, we identified mitofissin/Atg44, a mitochondrial intermembrane space-resident fission factor, which directly acts on lipid membranes and drives mitochondrial fission required for mitophagy in yeast. However, it remains unclear whether mitofissin is sufficient for mitophagy-associated mitochondrial fission and whether other factors act from outside mitochondria. Here, we identify a mitochondrial outer membrane-resident mitofissin-like microprotein required for mitophagy, and we name it mitofissin 2/Mfi2 based on the following results. Overexpression of an N-terminal Atg44-like region of Mfi2 induces mitochondrial fragmentation and partially restores mitophagy in atg44Δ cells. Mfi2 binds to lipid membranes and mediates membrane fission in a cardiolipin-dependent manner in vitro, demonstrating its intrinsic mitofissin activity. Coarse-grained molecular dynamics simulations further support the stable interaction of Mfi2 with cardiolipin-containing bilayers. Genetic analyses reveal that Mfi2 and the dynamin-related protein Dnm1 independently facilitate mitochondrial fission during mitophagy. Thus, Atg44 and Mfi2, two mitofissins with distinct localizations, are required for mitophagy-associated mitochondrial fission.
Source: EMBO Reports
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $7,990
Funders: Takeda Science Foundation, Institute for Fermentation, Osaka, Japan Agency for Medical Research and Development, Noda Institute for Scientific Research, Japan Society for the Promotion of Science, Japan Science and Technology Agency, RIKEN, Core Research for Evolutional Science and Technology
Awards: 多階層高次構造体群が駆動するオートファジーダイナミクス, G1127127438, G2576085165, G3252535643, Interdisciplinary research on autophagy: From working principles to pathophysiology, G4050521137, G4117653364, G4174427792, Elucidation of the mechanism of mitochondrial fission driven by novel factors, Theoretical study of autophagic membrane dynamics, 生体膜切断タンパク質ファミリーの同定と生体膜分裂における新たな概念の創出, A study on stress responses by co-creation of liquid-liquid phase separation and autophagy, Molecular mechanism of mitophagy driven by multidimensional phase separation, G5867970342, G5990166037, メンブレンアーゼAtg15の動的構造変化と膜脂質分解における活性制御機構, G6718509927, G7995332797, フェリチン液滴オートファジーの分子メカニズムの総合的理解, Regulation of receptor-mediated mitophagy and its physiological roles, ミトコンドリアの膜分裂の時空間制御機構の解明, Elucidation of physiological significance of mitophagy and its application to health science
OpenAlex ID: W7123338178