biostudies-literatureHe JThe National Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaThe Center for Advanced Interdisciplinary Science and Biomedicine of IHMThe Fundamental Research Funds from University of Science and Technology of Chinae3002247https://www.ebi.ac.uk/biostudies/studies/S-EPMC10465003biostudies-literatureUnknown21(8)Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) aPLoS biologyThe AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission.PMC10465003WK911000014191754106, 32070707, and 31621002QYPY202200032022YFA130310031872759Huang CLiu KZhao CHe JWang DXu CYan SChen JHWei WYao XDing LTang AHLiu XFang ZFu CHu LZheng FWu YfalseThe AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission.Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) a2023-01-01T00:00:00Z2023 Aug2025-04-04T19:23:45.397Z2025-04-04T19:23:45.397ZS-EPMC104650033759030210.1371/journal.pbio.3002247