A cyclic process: starting from the top, a mitochondrion can undergo fission (red lines) under certain conditions such as mtDNA damage or depolarization. This process is reversible, and one of the functional daughter mitochondria can fuse (blue lines) to a new one to recompose a larger organelle. Fission occurs with the severing of the inner and outer membranes (dotted line), and damaged components from the native organelle can be sorted toward segregated, dysfunctional mitochondria, subsequently targeted for mitophagy. This process can be transiently prevented by a reduced fission or a hyperfusion of several mitochondria that results in elongated organelles, as observed under mild starvation. The resulting elongated mitochondria (bottom) harbor more packed cristae and conserved bioenergetics and are excluded from mitophagy. Once the insult is resolved, hyperfused mitochondria undergo fission and fusion cycles to stabilize the native network.
