Figure 3. Overview of Mitochondrial Homeostasis.

Mitochondrial homeostasis is regulated through multiple steps that preserve a healthy network of mitochondria (green). Mitochondrial damage causes fragmentation (fission), regulated by the large GTPases dynamin-like protein 1 (Drp1) and dynamin 2 (Dnm2). Importantly, fission results in segregation of the damaged mitochondrial remnants (red). If not repaired, these remnants are isolated for degradation through mitochondrial autophagy (mitophagy). The mitochondria are encapsulated by a double membrane autophagosome (A) containing microtubule-associated proteins 1A/1B (LC3). These autophagosomes merge with a lysosome (L) where the acidic environment and lysosomal enzymes degrade and recycle the mitochondria. Healthy mitochondria continually fuse, mixing lipids, proteins, and mtDNA using mitofusin 1 and 2 (Mfn1 and Mfn2) for outer mitochondrial membrane fusion and Opa1 for inner mitochondrial membrane fusion. New components are added to expand and replenish mitochondrial networks through mitochondrial biogenesis, a process that involves both mitochondrial and nuclear transcription and translation, lipid synthesis, and replication of the mitochondrial genome.