Mitophagy

Mitochondria are highly plastic and dynamic organelles that have graded responses to the changing cellular, environmental, and developmental cues. Mitochondria mitophagy constant mitochondrial fission and fusion, mitophagy, mitochondrial biogenesis, and mitophagy, which coordinately control mitochondrial morphology, quantity, quality, turnover, and inheritance.

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

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. Recent progress in mitophagy studies reveals that mitochondrial priming is mediated either by the Pink1-Parkin signaling pathway or the mitophagic receptors Nix and Bnip3. In this review, we summarize our current knowledge on the mechanisms of mitophagy. We also discuss the pathophysiological roles of mitophagy and current assays used to monitor mitophagy. Macroautophagy hereafter referred to as autophagy is a genetically programmed, evolutionarily conserved catabolic process that degrades cellular proteins, and damaged or excessive organelles through the formation of a double-membrane structure known as the autophagosome Mizushima, ; Nakatogawa et al. Autophagosomes then fuse with lysosomes to form autolysosomes where the enveloped contents are degraded. The important roles of these Atg complexes in regulating autophagy have been extensively reviewed Ravikumar et al.

Cho, D. Mitophagy, in advanced plaques, mitophagy, VSMCs have shown athero-protective plaque-stabilizing properties, as their apoptosis or senesce promotes cap thinning, resulting in plaque instability [ ].

Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress. Mitophagy is key in keeping the cell healthy. It promotes turnover of mitochondria and prevents accumulation of dysfunctional mitochondria which can lead to cellular degeneration. Mitophagy is regulated by PINK1 and parkin proteins. In addition to the selective removal of damaged mitochondria, mitophagy is also required to adjust mitochondrial numbers to changing cellular metabolic needs, for steady-state mitochondrial turnover, and during certain cellular developmental stages, such as during cellular differentiation of red blood cells.

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. Recent progress in mitophagy studies reveals that mitochondrial priming is mediated either by the Pink1-Parkin signaling pathway or the mitophagic receptors Nix and Bnip3.

Mitophagy

Federal government websites often end in. The site is secure. Killackey et al. Mitophagy is an evolutionarily conserved process involving the autophagic targeting and clearance of mitochondria destined for removal. In this review, we highlight recent studies that have changed the way mitophagy is understood, from initiation through lysosomal degradation. We outline the numerous mitophagic receptors and triggers, with a focus on basal and physiologically relevant cues, offering insight into why they lead to mitochondrial removal. We also explore how mitophagy maintains mitochondrial homeostasis at the organ and system levels and how a loss of mitophagy may play a role in a diverse group of diseases, including cardiovascular, metabolic, and neurodegenerative diseases. With disrupted mitophagy affecting such a wide array of physiological processes, a deeper understanding of how to modulate mitophagy could provide avenues for numerous therapies. Mitophagy is one form of macroautophagy that involves selectively targeting and engulfing mitochondria for removal through lysosomal degradation Rodriguez-Enriquez et al.

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Wu, H. These results demonstrated the integration of stress signals and the coordinated execution of graded responses in response to mitochondrial stress conditions Ma K. Epilepsy Epilepsy is a complex, multifactorial disease, generally defined by its main symptom, which is frequent and repetitive seizures happening at random, and is subdivided into two syndrome categories: generalized and partial or localization-related. Evidence on the association between abnormal mitophagy and human neurological and psychiatric disorders has been summarized in Table 1. How these molecular machineries sense cellular stresses and how these complex mitochondrial behaviors are coordinated at the molecular level remains elusive. This effect is dependent on the activation by high glucose HG of the thioredoxin-Interacting Protein TXNIP , a protein that binds to thioredoxin Trx and inhibits its antioxidant activity, triggering cellular oxidative stress [ , ], as observed in diabetic rat retina in vivo and in vitro and in retinal endothelial cells in culture [ , , ]. Nature , 95— Therefore, it seems that mitochondrial fission is essential for mitophagy. Bibcode : iSci Shu X. The importance of mitophagy was demonstrated by the deletion of Beclin 1 and LC3b autophagy-associated genes in bone marrow-derived macrophages BMDM. Autophagy 4, — Grootaert M. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. Bcl-2 proteins and calcium signaling: complexity beneath the surface.

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Cell 21, — Aging 11, — In yeast, mitophagy selectively occurs in post-log phase cells under respiratory conditions. PMC Nature , 95— As mentioned, autophagy-independent pathways are likely also involved in the elimination of mitochondria in this process Schweers et al. NF-kappaB restricts inflammasome activation via elimination of damaged mitochondria. West, A. Shao Z. Kirkpatrick B. Cell 74, — Trends Biochem Sci. Autophagy machinery in the context of mammalian mitophagy.