Molecular mechanisms and physiological functions of mitophagy

Abstract

Degradation of mitochondria via a selective form of autophagy, named mitophagy, is a fundamental mechanism conserved from yeast to humans that regulates mitochondrial quality and quantity control. Mitophagy is promoted via specific mitochondrial outer membrane receptors, or ubiquitin molecules conjugated to proteins on the mitochondrial surface leading to the formation of autophagosomes surrounding mitochondria. Mitophagy-mediated elimination of mitochondria plays an important role in many processes including early embryonic development, cell differentiation, inflammation, and apoptosis. Recent advances in analyzing mitophagy in vivo also reveal high rates of steady-state mitochondrial turnover in diverse cell types, highlighting the intracellular housekeeping role of mitophagy. Defects in mitophagy are associated with various pathological conditions such as neurodegeneration, heart failure, cancer, and aging, further underscoring the biological relevance. Here, we review our current molecular understanding of mitophagy, and its physiological implications, and discuss how multiple mitophagy pathways coordinately modulate mitochondrial fitness and populations.

Rapamycin protects against aristolochic acid nephropathy in mice by potentiating mammalian target of rapamycin‑mediated autophagy

“…Autophagy and apoptosis are two important cellular processes that involve complex and intersecting protein networks ( 34 ). Autophagy promotes cell survival by accelerating cellular metabolism and assisting the removal of mitochondria following cellular injury, which can regulate apoptosis ( 35 ). Mitochondrial damage induces the release of metabolic hydrolase and caspase activator into the cytoplasm from the mitochondria, which degrades certain proteins in the cytoplasm and induces apoptosis ( 36 ).…”

Quality Matters? The Involvement of Mitochondrial Quality Control in Cardiovascular Disease

“…Aging is an irreversible biological process that typically involves the gradual deterioration of cardiac function and provokes various cardiovascular diseases through telomere shortening, genomic instability, oxidative stress, lipotoxicity, metabolic dysregulation, apoptosis, and mitophagy (Ren and Zhang, 2018;Ajoolabady et al, 2020;Onishi et al, 2021). Among these pathological etiologies, recent evidence has drawn light on and proposed that quality control through mitophagy plays a hand in the regulation of longevity and cardiovascular function in aging (Ren et al, 2017;Fernández et al, 2018;Nakamura and Yoshimori, 2018).…”

Mechanisms and Functions of Pexophagy in Mammalian Cells

“…For example, NBR1 and p62 are known to act as ubiquitin-binding receptors for several other selective autophagy, such as aggrephagy and xenophagy [ 13 ]. Specific receptors recognize a particular cargo, such as those receptors involved in mitophagy (BNIP3, BNIP3 L, and FUNDC1) [ 51 ]. Hence, other specific pexophagy receptors remain to be identified.…”