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).