2. Mitophagy: Definition and molecular mechanisms
Mitophagy, also known as mitochondrial autophagy, governs the removal of
long-lived, damaged/depolarized mitochondria, making it cardinal to
mitochondrial and cellular homeostasis (Zhou, Zhu, Wang, Zhu, Ren &
Chen, 2018). Mitophagy process also plays a key role in development, for
example removal of unnecessary mitochondria during erythropoiesis (Barde
et al., 2013), or adaptation to changing nutrient conditions. Mitophagy
and mitochondrial dynamics including fission and fusion dominate
mitochondria reconstruction (Hernandez‐Resendiz, Prunier, Girao, Dorn,
Hausenloy & Action, 2020). Mitophagy also wards off mitochondrial
apoptosis by engulfing/neutralizing long-lived or damaged mitochondria.
Therefore, defective mitophagy culminates in accumulation of impaired
mitochondria, thus evoking onset of chronic diseases such as cancer,
neurodegenerative, liver, and cardiovascular diseases.
Mechanistically, macroautophagy/autophagy involves the formation of a
transient double-membraned structure, termed a “phagophore” that
sequesters cytoplasm, including mitochondrial compartments (Wu, Zhang &
Ren, 2019). Upon completion, phagophores close to generate
“autophagosomes” or, in the case of mitophagy, “mitophagosomes”.
Eventually, autophagosomes or mitophagosomes fuse with lysosomes,
leading to degradation and recycling of the cargo content (Fig. 1).