RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

Abstract

Mitochondria are potential targets for the treatment of cardio-cerebrovascular ischemiareperfusion (I/R) injury. However, the role of the mitofusin 2 (Mfn2) protein in regulating mitochondrial fusion and cell survival has not been investigated. In the present study, an adenovirus-mediated Mfn2 overexpression assay was performed to understand the effects of Mfn2 on mitochondrial function and cell damage during cardiocerebrovascular I/R injury. After exposure to I/R injury in vitro, the transcription and expression of Mfn2 were significantly downregulated, which correlated with decreased cell viability and increased apoptosis. By contrast, overexpression of Mfn2 significantly repressed I/R-mediated cell death through modulation of glucose metabolism and oxidative stress. Furthermore, Mfn2 overexpression improved mitochondrial fusion in cells, an effect that was followed by increased mitochondrial membrane potential, improved mitophagy, and inhibition of mitochondria-mediated apoptosis. Our data also demonstrated that Mfn2 overexpression was associated with activation of the AMPK/Sirt3 signaling pathway. Inhibition of the AMPK/Sirt3 pathway abolished the protective effects of Mfn2 on I/R-induced cell injury arising from mitochondrial damage. Our results indicate that Mfn2 protects against cardio-cerebrovascular I/R injury by augmenting mitochondrial fusion and activating the AMPK/Sirt3 signaling pathway.

RETRACTED ARTICLE: Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury

“…Specifically, Janus-activated kinase 2(JAK2)/STAT3 pathway plays a functional role in blocking cell apoptosis induced by CI/RI [ 15 ]. Mitofusin-2 (Mfn2) is a mitochondrial fusion factor that could protect against cardio-cerebrovascular I/RI [ 16 ] and ameliorate hypoxia-induced neuronal apoptosis in ischemic brain damage [ 17 ]. It has been also recorded that Mfn2 exerts protective effect on CI/RI [ 18 ].…”

Novel Insights and Current Evidence for Mechanisms of Atherosclerosis: Mitochondrial Dynamics as a Potential Therapeutic Target

“…Therefore, mitochondrial fusion may have some compensatory effects on mtDNA mutation ( Chen et al, 2010 ). Liu et al (2020) found that overexpression of Mfn2 can increase MMP, enhance mitochondrial fusion, reduce mitoROS accumulation, activate the AMPK/SIRT3 signaling pathway, and prevent cardio-cerebrovascular ischemia/reperfusion (I/R) damage.…”

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

“…It should be emphasized that mfn1 and mfn2 play a controversial part in the regulation of mitophagy [ 41 ]. Depletion of both mfn1 and mfn2 in murine cardiomyocytes caused the accumulation of defective mitochondria by inhibiting mitophagy [ 42 ]. In contrast, an active role of mfn2 in preventing mitophagy was also proposed, associating with the maintenance of ER-mitochondrial contacts [ 43 ].…”