Tabara 2024 Cell
| Tábara LC, Burr SP, Frison M, Chowdhury SR, Paupe V, Nie Y, Johnson M, Villar-Azpillaga J, Viegas F, Segawa M, Anand H, Petkevicius K, Chinnery PF, Prudent J (2024) MTFP1 controls mitochondrial fusion to regulate inner membrane quality control and maintain mtDNA levels. Cell [Epub ahead of print]. https://doi.org/10.1016/j.cell.2024.05.017 |
Tabara Luis Carlos, Burr Stephen P, Frison Michele, Chowdhury Suvagata R, Paupe Vincent, Nie Yu, Johnson Mark, Villar-Azpillaga Jara, Viegas Filipa, Segawa Mayuko, Anand Hanish, Petkevicius Kasparas, Chinnery Patrick F, Prudent Julien (2024) Cell
Abstract: Mitochondrial dynamics play a critical role in cell fate decisions and in controlling mtDNA levels and distribution. However, the molecular mechanisms linking mitochondrial membrane remodeling and quality control to mtDNA copy number (CN) regulation remain elusive. Here, we demonstrate that the inner mitochondrial membrane (IMM) protein mitochondrial fission process 1 (MTFP1) negatively regulates IMM fusion. Moreover, manipulation of mitochondrial fusion through the regulation of MTFP1 levels results in mtDNA CN modulation. Mechanistically, we found that MTFP1 inhibits mitochondrial fusion to isolate and exclude damaged IMM subdomains from the rest of the network. Subsequently, peripheral fission ensures their segregation into small MTFP1-enriched mitochondria (SMEM) that are targeted for degradation in an autophagic-dependent manner. Remarkably, MTFP1-dependent IMM quality control is essential for basal nucleoid recycling and therefore to maintain adequate mtDNA levels within the cell. • Keywords: IMM quality control, IMM remodeling, MTFP1, Autophagy, Fission and fusion, Mitochondria, Mitochondrial dynamics, Mitophagy, mtDNA • Bioblast editor: Plangger M
Labels: MiParea: Respiration, mt-Structure;fission;fusion, mtDNA;mt-genetics, Genetic knockout;overexpression
Organism: Human
Preparation: Intact cells
Coupling state: ET, LEAK, ROUTINE
Pathway: ROX
HRR: Oxygraph-2k
2024-06
