PT - JOURNAL ARTICLE AU - Singh, Gaurav AU - Vengayil, Vineeth AU - Khanna, Aayushee AU - Adhikary, Swagata AU - Laxman, Sunil TI - Active control of mitochondrial network morphology by metabolism driven redox state AID - 10.1101/2024.08.05.606562 DP - 2024 Jan 01 TA - bioRxiv PG - 2024.08.05.606562 4099 - http://biorxiv.org/content/early/2024/10/30/2024.08.05.606562.short 4100 - http://biorxiv.org/content/early/2024/10/30/2024.08.05.606562.full AB - Mitochondria are dynamic organelles that constantly change morphology. What controls mitochondrial morphology however remains unresolved. Using actively respiring yeast cells growing in distinct carbon sources, we find that mitochondrial morphology and activity are unrelated. Cells can exhibit fragmented or networked mitochondrial morphology in different nutrient environments independent of mitochondrial activity. Instead, mitochondrial morphology is controlled by the intracellular redox state, which itself depends on the nature of electron entry into the Electron Transport Chain (ETC)— through complex I/II, or directly to coenzyme Q/cytochrome c. In metabolic conditions where direct electron entry is high, reactive oxygen species (ROS) increase, resulting in an oxidized cytosolic environment and rapid mitochondrial fragmentation. Decreasing direct electron entry into the ETC genetically or chemically, or reducing the cytosolic environment rapidly restores networked morphologies. Using controlled disruptions of electron flow to alter ROS and redox state, we demonstrate minute-scale, reversible control between networked and fragmented forms in an activity independent manner. Mechanistically, the fission machinery through Dnm1 responds in minute-scale to redox state changes, preceding the change in mitochondrial form. Thus, the metabolic state of the cell and its consequent cellular redox state actively controls mitochondrial form.Competing Interest StatementThe authors have declared no competing interest.