Mitophagy

Mitochondrial dysfunction constitutes one of the hallmarks of aging and is characterized by irregular mitochondrial morphology, mitophagy, insufficient ATP production, mitophagy, accumulation of mitochondrial DNA mtDNA mutations, increased production of mitochondrial reactive oxygen species ROS and mitophagy technic launcher oxidative damage to nucleic acids, proteins and lipids. Mitophagy, a mitochondrial quality control mechanism enabling the degradation of damaged and superfluous mitochondria, prevents such detrimental effects and reinstates cellular homeostasis in response mitophagy stress.

Federal government websites often end in. The site is secure. Mitophagy is a selective autophagic process, essential for cellular homeostasis, that eliminates dysfunctional mitochondria. Activated by inner membrane depolarization, it plays an important role during development and is fundamental in highly differentiated post-mitotic cells that are highly dependent on aerobic metabolism, such as neurons, muscle cells, and hepatocytes. Pharmacological or dietary interventions that restore mitophagy homeostasis and facilitate the elimination of irreversibly damaged mitochondria, thus, could serve as potential therapies in several chronic diseases. However, despite extraordinary advances in this field, mainly derived from in vitro and preclinical animal models, human applications based on the regulation of mitochondrial quality in patients have not yet been approved.

Mitophagy

Mitochondria are highly plastic and dynamic organelles that have graded responses to the changing cellular, environmental, and developmental cues. Mitochondria undergo constant mitochondrial fission and fusion, mitochondrial biogenesis, and mitophagy, which coordinately control mitochondrial morphology, quantity, quality, turnover, and inheritance. Mitophagy is a cellular process that selectively removes the aged and damaged mitochondria via the specific sequestration and engulfment of mitochondria for subsequent lysosomal degradation. It plays a pivotal role in reinstating cellular homeostasis in normal physiology and conditions of stress. Damaged mitochondria may either instigate innate immunity through the overproduction of ROS or the release of mtDNA, or trigger cell death through the release of cytochrome c and other apoptogenic factors when mitochondria damage is beyond repair. Distinct molecular machineries and signaling pathways are found to regulate these mitochondrial dynamics and behaviors. It is less clear how mitochondrial behaviors are coordinated at molecular levels. BCL2 family proteins interact within family members to regulate mitochondrial outer membrane permeabilization and apoptosis. They were also described as global regulators of mitochondrial homeostasis and mitochondrial fate through their interaction with distinct partners including Drp1, mitofusins, PGAM5, and even LC3 that involved mitochondrial dynamics and behaviors. In this review, we summarize recent findings on molecular pathways governing mitophagy and its coordination with other mitochondrial behaviors, which together determine cellular fate. Mitochondria are both the major source and the main targets of reactive oxygen species ROS. Under homeostatic conditions, mitochondrial ROS serve as retrograde signaling molecules for cell growth Diebold and Chandel, However, in conditions of stress or aging, mitochondrial ROS elicit oxidative damage to mitochondrial proteins, lipids, and DNA mtDNA , causing the malfunction of mitochondria. Dysfunctional mitochondria may produce even more ROS via vicious cycle that further amplify the release of ROS and mtDNA into the cytosol, which in turn can act as instigators of inflammation Nakahira et al. Non-reparable and severe damage of mitochondria leads to the release from the intermembrane space into the cytosol of cytochrome c and other pro-death factors Sinha et al.

MTORC1 regulates both general autophagy and mitophagy induction after oxidative phosphorylation uncoupling.

Federal government websites often end in. The site is secure. Mitochondria are essential organelles that regulate cellular energy homeostasis and cell death. The removal of damaged mitochondria through autophagy, a process called mitophagy, is thus critical for maintaining proper cellular functions. Indeed, mitophagy has been recently proposed to play critical roles in terminal differentiation of red blood cells, paternal mitochondrial degradation, neurodegenerative diseases, and ischemia or drug-induced tissue injury. Removal of damaged mitochondria through autophagy requires two steps: induction of general autophagy and priming of damaged mitochondria for selective autophagic recognition.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Maintaining optimal mitochondrial function is a feature of health.

Mitophagy

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.

Hestia figure amazon

Effects of exercise on obesity-induced mitochondrial dysfunction in skeletal muscle. Aberrant mitophagy in neurodegenerative and neuropsychiatric diseases. Atg32 also binds to Atg11, a selective autophagy receptor important for cargo selection Yorimitsu and Klionsky, and autophagosome formation by acting as a scaffold protein, which further recruits other autophagy proteins to form the autophagosome. It is also more objective and quantitative. A pseudo-receiver domain in Atg32 is required for mitophagy. Ravenhill, B. Heart Fail. Zanon A. Wang, C. Koop, E.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer.

Many known tumor suppressor genes such as Lkt , Ampk , and Pten are positive regulators of autophagy Cully et al. Changes of mitochondria in atherosclerosis: Possible determinant in the pathogenesis of the disease. J Biol Chem. Development As discussed above, mitophagy plays an essential role in erythrocyte differentiation and maturation. Hamilton, M. Du, C. Autophagy 10, — It is currently not clear whether other factors also regulate citrate synthase activity. Foxo3 controls autophagy in skeletal muscle in vivo. Nat Med. Mitophagy mediated by dct-1, the ortholog of NIX, plays an important role during C. Finally, increased numbers of depolarized mitochondria and mitophagy were observed in fibroblasts derived from patients deficient in coenzyme CoQ , a small lipophilic molecule critical for the transport of electrons from complexes I and II to complex III in the mitochondrial respiratory chain. Turco, E. Mitochondria and aging.