Mitochondrial degradation: Mitophagy and beyond

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(19), P. 3404 - 3420

Published: Oct. 1, 2023

Mitochondria are central hubs of cellular metabolism that also play key roles in signaling and disease. It is therefore fundamentally important mitochondrial quality activity tightly regulated. Mitochondrial degradation pathways contribute to control networks can regulate the metabolic profile mitochondria ensure homeostasis. Here, we cover many varied ways which cells degrade or remove their unwanted mitochondria, ranging from mitophagy extrusion. The molecular signals driving these discussed, including physiological contexts under different engaged.

Language: Английский

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PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 7, 2023

Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause mitochondrial membrane potential (ΔΨm) depolarization, trigger the mitochondria-dependent intrinsic pathway, lead to osteoblast ultimately osteopenia microstructural destruction. In this study, we found AOPPs also induced ROS (mtROS) generation osteoblastic MC3T3-E1 cells, which was closely related NOX-derived ROS, aggravated oxidative stress condition, thereby further promoting apoptosis. Removing excessive damaged mitochondria is key factor reversing AOPP-induced Here, by vitro studies, showed rapamycin activated PINK1/Parkin-mediated mitophagy AOPP-stimulated cells significantly alleviated cell eliminating mitochondria. vivo studies decrease plasma AOPP concentration inhibit apoptosis, thus ameliorating accumulation-related loss, destruction mineral density (BMD) loss. Together, our indicated therapeutic strategies aimed at upregulating preserving function might have for treating

Language: Английский

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Mitophagy and cGAS–STING crosstalk in neuroinflammation

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(8), P. 3327 - 3361

Published: May 13, 2024

Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS–STING pathway, crucial innate immunity. This pathway responds DNA and associated with cellular stress. Our review explores molecular details regulatory mechanisms of mitophagy pathway. We critically evaluated literature demonstrating how dysfunctional leads neuroinflammatory conditions, primarily through accumulation mitochondria, activating activation prompts production proinflammatory cytokines, exacerbating neuroinflammation. emphasizes interaction between Effective might suppress offering protection against Conversely, impaired may activate potentially leading chronic Additionally, we explored this influences neurodegenerative disorders, suggesting a common mechanism in such diseases. In conclusion, there need additional targeted research unravel complexities mitophagy–cGAS–STING interactions their role neurodegeneration. highlights potential therapies targeting these pathways, which could lead new treatments conditions. synthesis enhances our understanding foundations neuroinflammation opens therapeutic avenues disease research.

Language: Английский

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BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(11)

Published: Nov. 17, 2022

Abstract Mitophagy is an important metabolic mechanism that modulates mitochondrial quality and quantity by selectively removing damaged or unwanted mitochondria. BNIP3 (BCL2/adenovirus e1B 19 kDa protein interacting 3), a outer membrane protein, mitophagy receptor mediates under various stresses, particularly hypoxia, since hypoxia-responsive protein. However, the underlying mechanisms regulate thus mediate hypoxic conditions remain elusive. Here, we demonstrate in hypoxia JNK1/2 (c-Jun N-terminal kinase 1/2) phosphorylates at Ser 60/Thr 66, which hampers proteasomal degradation of drives facilitating direct binding to LC3 (microtubule-associated 1 light chain while PP1/2A (protein phosphatase 1/2A) represses dephosphorylating triggering its degradation. These findings reveal intrinsic cells use via JNK1/2-BNIP3 pathway response hypoxia. Thus, signaling strongly links may be promising therapeutic target for hypoxia-related diseases.

Language: Английский

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Relationship between ferroptosis and mitophagy in cardiac ischemia reperfusion injury: a mini-review

PeerJ, Journal Year: 2023, Volume and Issue: 11, P. e14952 - e14952

Published: March 13, 2023

Cardiovascular diseases (CVD), with high morbidity and mortality, seriously affect people’s life social development. Clinically, reperfusion therapy is typically used to treat ischemic cardiomyopathy, such as severe coronary heart disease acute myocardial infarction. However, can lead ischemia injury (MIRI), which the prognosis of patients. Studying mechanisms MIRI help us improve treatment MIRI. The pathological process involves many ferroptosis mitophagy. Ferroptosis exacerbate MIRI, regulation mitophagy alleviate Both are closely related ROS, but there no clear understanding relationship between In this review, we analyzed according role mTOR, NLPR3 HIF. addition, simultaneous may be superior single for We summarized potential drugs that regulate and/or ferroptosis, hoping provide reference development methods treatment.

Language: Английский

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Mitophagy in Alzheimer's disease and other metabolic disorders: a focus on mitochondrial-targeted therapeutics

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102732 - 102732

Published: March 1, 2025

Language: Английский

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Compositions and Functions of Mitochondria-Associated Endoplasmic Reticulum Membranes and Their Contribution to Cardioprotection by Exercise Preconditioning

Frontiers in Physiology, Journal Year: 2022, Volume and Issue: 13

Published: June 6, 2022

Mitochondria-associated endoplasmic reticulum membranes (MAMs) are important components of intracellular signaling and contribute to the regulation Ca 2+ /lipid homeostasis, mitochondrial dynamics, autophagy/mitophagy, apoptosis, inflammation. Multiple studies have shown that proteins located on MAMs mediate cardioprotection. Exercise preconditioning (EP) has been protect myocardium from adverse stimuli, but these mechanisms still being explored. Recently, a growing body evidence points MAMs, suggesting exercise or EP may be involved in cardioprotection by modulating subsequently affecting MAMs. In this review, we summarize latest findings analyzing structure function role MAM-related We focused possible which can modulate involvement found affect regulating changes MFN2, MFN1, AMPK, FUNDC1, BECN1, VDAC1, GRP75, IP3R, CYPD, GSK3β, AKT, NLRP3, GRP78, LC3, thus playing cardioprotective role. also provided direction for future interest so more in-depth conducted elucidate relationship between

Language: Английский

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N-acetyl-L-cysteine alleviates FUNDC1-mediated mitophagy by regulating mitochondrial dynamics in type 1 diabetic nephropathy canine

Life Sciences, Journal Year: 2022, Volume and Issue: 313, P. 121278 - 121278

Published: Dec. 12, 2022

Language: Английский

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Mitophagy in metabolic syndrome

Journal of Clinical Hypertension, Journal Year: 2023, Volume and Issue: 25(5), P. 397 - 403

Published: April 11, 2023

Abstract Metabolic syndrome (MS), a chronic and non‐communicable pathological condition, is characterized by constellation of clinical manifestations including insulin resistance, abdominal adiposity, elevated blood pressure, perturbations in lipid metabolism. The prevalence MS has increased dramatically both developed developing countries now become truly global problem. Excessive energy intake concomitant obesity are the main drivers this syndrome. Mitophagy, which cells degrade damaged mitochondria through selective form autophagy, assumes crucial position regulation mitochondrial integrity maintenance. Abnormal quality could result spectrum conditions related to metabolic dysfunction, syndrome, cardiovascular ailments, neoplasms. Recently, there been proliferation research pertaining process mitophagy context MS, various regulatory pathways like ubiquitin‐dependent mechanism receptor‐mediated mechanisms, among others. Furthermore, studies have uncovered that serves defensive function advancement Syndrome, inhibition exacerbates MS. As result, holds great promise as therapeutic approach management Syndrome. In comprehensive analysis, authors present synthesis diverse involved well its modes action disorders implicated development Including obesity, resistance (IR), type 2 diabetes mellitus (T2DM), offering novel avenues for prophylaxis

Language: Английский

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Epigenomic signature of major congenital heart defects in newborns with Down syndrome

Human Genomics, Journal Year: 2023, Volume and Issue: 17(1)

Published: Oct. 6, 2023

Congenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS), but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated CHDs in DS, comprehensive contribution epigenetic marks lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) DS major compared without CHDs.

Language: Английский

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