Figure 1.

The role of mitochondrial dynamics in mitochondrial heterogeneity. During the mitochondrial life cycle, mitochondrial heterogeneity primarily occurs at three main phases (from left to right): biogenesis, fusion/fission, and autophagy of mitochondria (mitophagy). (A) While increases in mitochondrial heterogeneity are beneficial to cellular health, sustained activity of the mitochondrial life cycle reduces mitochondrial heterogeneity. Specifically, fusion events result in the contents of two different mitochondria mixing, ultimately resulting in their contents becoming the same, equilibrating the mitochondrial population within the cell, and thereby decreasing intracellular heterogeneity. After fission, one daughter mitochondrion will depolarize (green) while the other will maintain normal membrane potential (red). Depolarized mitochondria will undergo one of two fates: either a transient depolarization will occur and they will slowly regain their membrane potential to fuse again (green mitochondria back to red), or they will remain depolarized and undergo mitophagy (the mitochondria will remain green). Mitophagy events remove depolarized mitochondria from the mitochondrial population, thereby reducing intracellular membrane potential heterogeneity. (B) Dysregulation and blockades within the mitochondrial life cycle lead to increases in heterogeneity. Impaired clearance of mitochondria with sustained depolarization, via mitophagy, increases the pre-autophagic pool. Increasing the pre-autophagic pool size increases intracellular heterogeneity, and the mitochondrial population now transitions from a population with a common membrane potential (red) to one with multiple membrane potentials (red and green).