Mitophagy

Federal government websites often end in. The site mitophagy secure. Mitophagy is a selective autophagic process, essential for cellular homeostasis, that eliminates dysfunctional mitochondria.

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.

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.

Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase mitophagy by eliminating IAP inhibition. Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and recruitment of Parkin in cardiac myocytes, mitophagy.

Mitochondrial dysfunction constitutes one of the hallmarks of aging and is characterized by irregular mitochondrial morphology, insufficient ATP production, accumulation of mitochondrial DNA mtDNA mutations, increased production of mitochondrial reactive oxygen species ROS and the consequent 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 to stress. To date, there is increasing evidence that mitophagy is significantly impaired in several human pathologies including aging and age-related diseases such as neurodegenerative disorders, cardiovascular pathologies and cancer. Therapeutic interventions aiming at the induction of mitophagy may have the potency to ameliorate these dysfunctions. In this review, we summarize recent findings on mechanisms controlling mitophagy and its role in aging and the development of human pathologies. Mitochondria are highly organized and dynamic organelles that undergo continuous fission and fusion Chen and Chan, ; Pham et al.

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. Mitochondria are dynamic organelles with multiple functions. They participate in necrotic cell death and programmed apoptotic, and are crucial for cell metabolism and survival. Mitophagy serves as a cytoprotective mechanism to remove superfluous or dysfunctional mitochondria and maintain mitochondrial fine-tuning numbers to balance intracellular homeostasis. Growing evidences show that mitophagy, as an acute tissue stress response, plays an important role in maintaining the health of the mitochondrial network.

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.

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Salidroside Sal is a phenylpropanoid glycoside extracted from Rhodiola [ ]. The innate and adaptive immune systems are able to sense pathogen-associated molecular patterns PAMPs and danger-associated molecular patterns DAMPs arising from exogenous clues including bacteria, virus, fungi, and parasites, as well as endogenous entities such as cancer cells and to mount defensive immune responses. Further research is needed to explore the patho- physiological roles of this molecular switch in response to environmental and cellular stresses. The regulation of autophagosome dynamics by huntingtin and HAP1 is disrupted by expression of mutant huntingtin, leading to defective cargo degradation. The removal of damaged or unwanted mitochondria, mitophagy was found to be essential for maintaining cellular fitness. Chen, L. Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features. In unhealthy mitochondria, the inner mitochondrial membrane becomes depolarized. Kazlauskaite, A. Mitophagy in neurodegenerative diseases.

Federal government websites often end in. The site is secure.

Moreover, it has been demonstrated that epilepsy or epileptic seizures can also result directly from impaired mitophagy. Mitophagy is necessary for myogenic differentiation, as demonstrated both in vitro, using C2C12 myoblasts [ ], and in vivo. ULK1 and Atg7 Similar mitochondrial clearance defects were observed in Atg7- or ULK1-deficient mice, further confirming the involvement of autophagy in this process Kundu et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. As mitochondria are essential organelles that regulate cellular energy metabolism and cell death, mitochondrial homeostasis has been linked to many pathophysiological conditions and diseases. Theoretically, removal of damaged mitochondria requires the formation of separate autophagosomes, which may then mobilize to the site where the damaged mitochondria are located. Resveratrol decreases oxidative stress by restoring mitophagy and improves the pathophysiology of dystrophin-deficient mdx mice. The resulting mutated RNA, when translated, forms toxic dipeptide-repeat polypeptides DPRs , which are possibly involved in the induced mitochondrial damage. It was initially found to be upregulated in mouse models of NAFLD, where it was found to foster mitochondrial damage and the inhibition of mitophagy. Balendra R. Enhanced mitophagy and mitochondrial turnover contributes to increased mitochondrial function and cellular activity.