AMPKα2 Protects Against the Development of Heart Failure by Enhancing Mitophagy via PINK1 Phosphorylation

Wang, Bei; Nie, Jiali; Wu, Lujin; Hu, Yangyang; Wen, Zheng; Dong, Lingli; Zou, Ming‐Hui; Chen, Chen; Wang, Dao Wen

doi:10.1161/circresaha.117.312317

Cited by 229 publications

(225 citation statements)

References 40 publications

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“…Mitochondrial fragmentation and damaged mitochondria can be cleared by a form of selective autophagy-mitophagy. Mitophagy is a specific class of autophagy eliminating dysfunctional mitochondria from the heart under normal physiological conditions and pathological stresses, maintaining healthy mitochondria at a stable number [42]. Mitochondrial fusion and mitophagy were observably suppressed by ischemia-reperfusion (I/R) injury, accompanied by myocardial inflammation, infarction area expansion, heart dysfunction, and cardiomyocyte oxidative stress [43].…”

Section: Mitochondrial Dysfunction In Cardiac Agingmentioning

confidence: 99%

“…The damaged mitochondria are sensed by the decreased mitochondrial membrane potential (ΔΨm) and transduced to Parkin via the autophosphorylation of PINK1 [45]. Ubiquitination of mitochondrial outer membrane proteins mediated by Parkin is an initial signal for autophagosome phagocytosis and subsequently progresses to lysosome degradation [42]. There were severe defects in mitochondrial homeostasis in PINK1 KO mice accompanied by changes in the mitochondrial network and an increase in ROS [46].…”

Section: Mitochondrial Dysfunction In Cardiac Agingmentioning

confidence: 99%

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Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Quan

Xin

Tian

et al. 2020

Oxidative Medicine and Cellular Longevity

130

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Mitochondrial DNA (mtDNA) damage is associated with the development of cardiovascular diseases. Cardiac aging plays a central role in cardiovascular diseases. There is accumulating evidence linking cardiac aging to mtDNA damage, including mtDNA mutation and decreased mtDNA copy number. Current wisdom indicates that mtDNA is susceptible to damage by mitochondrial reactive oxygen species (mtROS). This review presents the cellular and molecular mechanisms of cardiac aging, including autophagy, chronic inflammation, mtROS, and mtDNA damage, and the effects of mitochondrial biogenesis and oxidative stress on mtDNA. The importance of nucleoid-associated proteins (Pol γ), nuclear respiratory factors (NRF1 and NRF2), the cGAS-STING pathway, and the mitochondrial biogenesis pathway concerning the development of mtDNA damage during cardiac aging is discussed. Thus, the repair of damaged mtDNA provides a potential clinical target for preventing cardiac aging.

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Section: Mitochondrial Dysfunction In Cardiac Agingmentioning

confidence: 99%

Section: Mitochondrial Dysfunction In Cardiac Agingmentioning

confidence: 99%

Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Quan

Xin

Tian

et al. 2020

Oxidative Medicine and Cellular Longevity

130

View full text Add to dashboard Cite

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“…Overall, the emerging consensus from these studies is that basal and stress-induced mitophagy play a critical role in maintaining cardiac structure and function, and could be therapeutically targeted to achieve cardioprotection under stress (reviewed in (142)). Indeed, studies indicate suppression of mitophagy with prolonged cardiac stress, such as pressure overload, which can be rescued by stimulating autophagosome formation with Tat-Beclin-1 transduction (196) or enhancing AMPK2α-mediated PINK1 phorphorylation (225). Molecular players that mediate mitochondrial dynamics, namely mitofusins (MFN1 and MFN2) that mediate mitochondrial fusion; and Drp1, that mediates mitochondrial fission, play a critical role in maintaining mitochondrial quality control and regulating mitophagy in the heart (201, 203).…”

Section: Lysosomes As Regulators Of Cardiac Homeostasis and The Fastimentioning

confidence: 99%

Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss

Mani

Javaheri

Diwan

2018

Comprehensive Physiology

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Adaptive responses that counter starvation have evolved over millennia to permit organismal survival, including changes at the level of individual organelles, cells, tissues, and organ systems. In the past century, a shift has occurred away from disease caused by insufficient nutrient supply toward overnutrition, leading to obesity and diabetes, atherosclerosis, and cardiometabolic disease. The burden of these diseases has spurred interest in fasting strategies that harness physiological responses to starvation, thus limiting tissue injury during metabolic stress. Insights gained from animal and human studies suggest that intermittent fasting and chronic caloric restriction extend lifespan, decrease risk factors for cardiometabolic and inflammatory disease, limit tissue injury during myocardial stress, and activate a cardioprotective metabolic program. Acute fasting activates autophagy, an intricately orchestrated lysosomal degradative process that sequesters cellular constituents for degradation, and is critical for cardiac homeostasis during fasting. Lysosomes are dynamic cellular organelles that function as incinerators to permit autophagy, as well as degradation of extracellular material internalized by endocytosis, macropinocytosis, and phagocytosis. The last decade has witnessed an explosion of knowledge that has shaped our understanding of lysosomes as central regulators of cellular metabolism and the fasting response. Intriguingly, lysosomes also store nutrients for release during starvation; and function as a nutrient sensing organelle to couple activation of mammalian target of rapamycin to nutrient availability. This article reviews the evidence for how the lysosome, in the guise of a janitor, may be the "undercover boss" directing cellular processes for beneficial effects of intermittent fasting and restoring homeostasis during feast and famine. © 2018 American Physiological Society. Compr Physiol 8:1639-1667, 2018.

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“…Accordingly, the inhibition of mitophagy results in a surge in mitochondrial apoptotic signaling followed by death of HBV-infected hepatocytes [40]. In supportive, in the model of heart failure, the induction of mitophagy by activating AMPKalpha2-PINK1-Parkin signaling pathway results in mitochondrial depolarization, removal of damaged mitochondria, reduction of ROS production, improvement in mitochondrial function as well as decrease of apoptosis of cardiomyocytes [100]. Nevertheless, the consequences of mitophagy or apoptosis may be complicated.…”

Section: Challenges and Perspectivesmentioning

confidence: 99%

Operation of mitochondrial machinery in viral infection-induced immune responses

Lai

Luo

2018

Biochemical Pharmacology

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Mitochondria have been recognized as ancient bacteria that contain evolutionary endosymbionts. Metabolic pathways and inflammatory signals interact within mitochondria in response to different stresses, such as viral infections. In this commentary, we address several interesting questions, including (1) how do mitochondrial machineries participate in immune responses; (2) how do mitochondria mediate antiviral immunity; (3) what mechanisms involved in mitochondrial machinery, including the downregulation of mitochondrial DNA (mtDNA), disturbances of mitochondrial dynamics, and the induction of mitophagy and regulation of apoptosis, have been adopted by viruses to evade antiviral immunity; (4) what mechanisms involve the regulation of mitochondrial machineries in antiviral therapeutics; and (5) what are the potential challenges and perspectives in developing mitochondria-targeting antiviral treatments? This commentary provides a comprehensive review of the roles and mechanisms of mitochondrial machineries in immunity, viral infections and related antiviral therapeutics.

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AMPKα2 Protects Against the Development of Heart Failure by Enhancing Mitophagy via PINK1 Phosphorylation

Abstract: In failing hearts, the dominant AMPKα isoform switched from AMPKα2 to AMPKα1, which accelerated HF. The results show that phosphorylation of Ser495 in PINK1 by AMPKα2 was essential for efficient mitophagy to prevent the progression of HF.

Cited by 229 publications

References 40 publications

Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Mitochondrial ROS-Modulated mtDNA: A Potential Target for Cardiac Aging

Lysosomes Mediate Benefits of Intermittent Fasting in Cardiometabolic Disease: The Janitor Is the Undercover Boss

Operation of mitochondrial machinery in viral infection-induced immune responses

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