2026-01-13 九州大学
マイトファジー誘導時におけるミトコンドリア分裂モデル
<関連情報>
- https://www.kyushu-u.ac.jp/ja/researches/view/1391
- https://www.kyushu-u.ac.jp/f/64406/26_0113_01.pdf
- https://link.springer.com/article/10.1038/s44319-025-00689-x
ミトファジー中のミトコンドリア分裂には内側と外側のミトフィシンの両方が必要である Mitochondrial fission during mitophagy requires both inner and outer mitofissins
Kentaro Furukawa,Tatsuro Maruyama,Yuji Sakai,Shun-ichi Yamashita,Keiichi Inoue,Tomoyuki Fukuda,Nobuo N Noda & Tomotake Kanki
EMBO Reports Published:13 January 2026
DOI:https://doi.org/10.1038/s44319-025-00689-x
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.
