Role of Mitofusins and Mitophagy in Life or Death Decisions

Joaquim, Mariana; Escobar-Henriques, Mafalda

doi:10.3389/fcell.2020.572182

Cited by 36 publications

(31 citation statements)

References 320 publications

(425 reference statements)

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“…In the post-infarcted heart, liraglutide (a classical anti-diabetic drug) was found to reduce cardiac fibrosis, inhibit the inflammatory response, and prevent myocardial death by inhibiting Parkin-induced mitophagy ( Qiao et al, 2018 ). These findings suggest that excessive mitophagy can exacerbate cardiac injury ( Joaquim and Escobar-Henriques, 2020 ).…”

Section: The Dual Role Of Mitophagy In Myocardial Damagementioning

confidence: 99%

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

Kimberlee

et al. 2021

Front. Physiol.

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A variety of complex risk factors and pathological mechanisms contribute to myocardial stress, which ultimately promotes the development of cardiovascular diseases, including acute cardiac insufficiency, myocardial ischemia, myocardial infarction, high-glycemic myocardial injury, and acute alcoholic cardiotoxicity. Myocardial stress is characterized by abnormal metabolism, excessive reactive oxygen species production, an insufficient energy supply, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. Mitochondria, the main organelles contributing to the energy supply of cardiomyocytes, are key determinants of cell survival and death. Mitophagy is important for cardiomyocyte function and metabolism because it removes damaged and aged mitochondria in a timely manner, thereby maintaining the proper number of normal mitochondria. In this review, we first introduce the general characteristics and regulatory mechanisms of mitophagy. We then describe the three classic mitophagy regulatory pathways and their involvement in myocardial stress. Finally, we discuss the two completely opposite effects of mitophagy on the fate of cardiomyocytes. Our summary of the molecular pathways underlying mitophagy in myocardial stress may provide therapeutic targets for myocardial protection interventions.

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Section: The Dual Role Of Mitophagy In Myocardial Damagementioning

confidence: 99%

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

Kimberlee

et al. 2021

Front. Physiol.

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“…Among others, our previous finding evidenced a possible role of mitochondrial dynamics in the control of cellular health and functionality in different tissues [55,80], suggesting the importance of studying these physiological mechanisms, mainly in the liver, that play a key role in lipid metabolism as well as in detoxification processes against external toxic agents [81]. We chose to analyze MFN2 because it has also been suggested that MFN2 is a protective target in the liver, as it controls the physiological balance between apoptosis and autophagy in liver failure [82]. As far as we know, this is the first time that mitochondrial proteins involved in mitochondrial dynamic behaviour are investigated in response to increasing doses of DDE in HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins

Burgos-Aceves

Migliaccio

Lepretti

et al. 2021

Toxics

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Dichlorodiphenyldichloroethylene (DDE), the primary persistent metabolite of dichlorodiphenyltrichloroethane (DDT), has toxic effects on cells, but its dose-dependent impact on mitochondrial proteins involved in mitochondrial fusion and fission processes associated with cell viability impairment has not yet been analysed. Mitochondrial fusion and fission processes are critical to maintaining the mitochondrial network and allowing the cell to respond to external stressors such as environmental pollutants. Fusion processes are associated with optimizing mitochondrial function, whereas fission processes are associated with removing damaged mitochondria. We assessed the effects of different DDE doses, ranging between 0.5 and 100 µM, on cell viability and mitochondrial fusion/fission proteins in an in vitro hepatic cell model (human hepatocarcinomatous cells, HepG2); the DDE induced a decrease in cell viability in a dose-dependent manner, and its effect was enhanced in conditions of coincubation with dietary fatty acids. Fusion protein markers exhibited an inverted U-shape dose-response curve, showing the highest content in the 2.5–25 μM DDE dose range. The fission protein marker was found to increase significantly, leading to an increased fission/fusion ratio with high DDE doses. The low DDE doses elicited cell adaption by stimulating mitochondrial dynamics machinery, whereas high DDE doses induced cell viability loss associated with mitochondrial dynamics to shift toward fission. Present results are helpful to clarify the mechanisms underlying the cell fate towards survival or death in response to increasing doses of environmental pollutants.

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“…Our present data showed DHA pretreatment upregulated the protein levels of mitophagy-specific molecules in astrocytes at 12 hours after hypoxia, suggesting that the mitochondrial protection from ischemic/reperfusion stress by DHA is to some extent due to mitophagy enhancement. Another reactive mitochondrial quality control is reshaped by fusion and fission [ 34 , 40 ]. The result demonstrated an upregulation of mfn1 and mfn2 (mitofusin-specific protein), which indicated that DHA promoted mitochondrial fusion in the hypoxia-treated astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Supplemental N‐3 Polyunsaturated Fatty Acids Limit A1‐Specific Astrocyte Polarization via Attenuating Mitochondrial Dysfunction in Ischemic Stroke in Mice

Cao

Dong

Luo

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ischemic stroke is one of the leading causes of death and disability for adults, which lacks effective treatments. Dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) exerts beneficial effects on ischemic stroke by attenuating neuron death and inflammation induced by microglial activation. However, the impact and mechanism of n-3 PUFAs on astrocyte function during stroke have not yet been well investigated. Our current study found that dietary n-3 PUFAs decreased the infarction volume and improved the neurofunction in the mice model of transient middle cerebral artery occlusion (tMCAO). Notably, n-3 PUFAs reduced the stroke-induced A1 astrocyte polarization both in vivo and in vitro. We have demonstrated that exogenous n-3 PUFAs attenuated mitochondrial oxidative stress and increased the mitophagy of astrocytes in the condition of hypoxia. Furthermore, we provided evidence that treatment with the mitochondrial-derived antioxidant, mito-TEMPO, abrogated the n-3 PUFA-mediated regulation of A1 astrocyte polarization upon hypoxia treatment. Together, this study highlighted that n-3 PUFAs prevent mitochondrial dysfunction, thereby limiting A1-specific astrocyte polarization and subsequently improving the neurological outcomes of mice with ischemic stroke.

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Role of Mitofusins and Mitophagy in Life or Death Decisions

Cited by 36 publications

References 320 publications

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

Dose-Dependent Response to the Environmental Pollutant Dichlorodipheniletylhene (DDE) in HepG2 Cells: Focus on Cell Viability and Mitochondrial Fusion/Fission Proteins

Supplemental N‐3 Polyunsaturated Fatty Acids Limit A1‐Specific Astrocyte Polarization via Attenuating Mitochondrial Dysfunction in Ischemic Stroke in Mice

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