Lhuissier 2024 iScience
| Lhuissier C, Desquiret-Dumas V, Girona A, Alban J, Faure J, Cassereau J, Codron P, Lenaers G, Baris OR, Gueguen N, Chevrollier A (2024) Mitochondrial F0F1-ATP synthase governs the induction of mitochondrial fission. iScience 27:109808. https://doi.org/10.1016/j.isci.2024.109808 |
Lhuissier Charlene, Desquiret-Dumas Valerie, Girona Anais, Alban Jennifer, Faure Justine, Cassereau Julien, Codron Philippe, Lenaers Guy, Baris Olivier R, Gueguen Naig, Chevrollier Arnaud (2024) iScience
Abstract: Mitochondrial dynamics is a process that balances fusion and fission events, the latter providing a mechanism for segregating dysfunctional mitochondria. Fission is controlled by the mitochondrial membrane potential (ΞΞ¨m), optic atrophy 1 (OPA1) cleavage, and DRP1 recruitment. It is thought that this process is closely linked to the activity of the mitochondrial respiratory chain (MRC). However, we report here that MRC inhibition does not decrease ΞΞ¨m nor increase fission, as evidenced by hyperconnected mitochondria. Conversely, blocking F0F1-ATP synthase activity induces fragmentation. We show that the F0F1-ATP synthase is sensing the inhibition of MRC activity by immediately promoting its reverse mode of action to hydrolyze matrix ATP and restoring ΞΞ¨m, thus preventing fission. While this reverse mode is expected to be inhibited by the ATPase inhibitor ATPIF1, we show that this sensing is independent of this factor. We have unraveled an unexpected role of F0F1-ATP synthase in controlling the induction of fission by sensing and maintaining ΞΞ¨m. β’ Keywords: Biochemistry, Cell biology, Functional aspects of cell biology β’ Bioblast editor: Plangger M β’ O2k-Network Lab: FR Angers Gueguen N
Labels: MiParea: Respiration, mt-Structure;fission;fusion
Organism: Mouse
Tissue;cell: Fibroblast
Preparation: Permeabilized cells, Intact cells
Regulation: mt-Membrane potential Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N, NS, ROX HRR: Oxygraph-2k, O2k-Fluorometer
2024-05, TMRM
