Deacetylation of mitofusin-2 by sirtuin-1: A critical event in cell survival after ischemia

Lee, Sooyeon; Go, Kristina L.; Kim, Jae-Sung

doi:10.1080/23723556.2015.1087452

Cited by 11 publications

(19 citation statements)

References 10 publications

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“…4A and C ). Furthermore, several studies have suggested that Sirtuin 1 (SIRT1) is the upstream inducer of Mfn2 expression ( 45 ), and therefore, we aimed to ascertain whether SIRT1 is involved in Mfn2 regulation by Yap. Firstly, we found that loss of Yap was associated with the downregulation of SIRT1 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy

et al. 2018

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Gastric cancer is the fifth most common cancer worldwide and Hippo-Yap is the novel signaling pathway which plays an important role in gastric cancer tumor development and progression. However, little insight is available to date regarding the specific role of Yes-associated protein (Yap) in gastric cancer. In the present study, we identified the mechanism through which Yap sustains gastric cancer viability and migration. Yap was greatly upregulated in gastric cancer cells and its expression promoted cellular migration and survival. Functional studies found that knockdown of Yap reduced the mitophagy activity, which subsequently caused mitochondrial apoptosis and cellular oxidative stress. The latter impaired adhesive protein expression, alleviated F-actin expression, blunted lamellipodium formation, leading to inhibition of cancer cell motility. Mechanistically, Yap preserved Sirtuin 1 (SIRT1) activity which manipulated mitofusin 2 (Mfn2) expression and subsequent mitophagy. Loss of Yap reduced SIRT1 expression and inhibited Mfn2-mediated mitophagy. Collectively, our results identified Hippo-Yap as a tumor promoter in gastric cancer that was mediated via activation of the SIRT1/Mfn2/mitophagy axis, with potential applications to gastric cancer therapy involving cancer survival and migration.

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Section: Resultsmentioning

confidence: 99%

Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy

et al. 2018

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“…These findings suggest that nucleo-cytoplasmic shuttling of Sirt1 and Sirt1–Rb co-localization play an important role in HX-induced OPC proliferation. Since the predominantly nuclear Sirt1 also regulates basal proliferation, it is possible that HX-induced Sirt1 translocation need not be restricted to proliferation, and suggests inclusion of metabolic targets, including mitofusin-2, whose deacetylation regulates mitochondrial function and cell death after ischaemic/reperfusion injury59.…”

Section: Discussionmentioning

confidence: 99%

Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury

et al. 2016

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Regenerative processes in brain pathologies require the production of distinct neural cell populations from endogenous progenitor cells. We have previously demonstrated that oligodendrocyte progenitor cell (OPC) proliferation is crucial for oligodendrocyte (OL) regeneration in a mouse model of neonatal hypoxia (HX) that reproduces diffuse white matter injury (DWMI) of premature infants. Here we identify the histone deacetylase Sirt1 as a Cdk2 regulator in OPC proliferation and response to HX. HX enhances Sirt1 and Sirt1/Cdk2 complex formation through HIF1α activation. Sirt1 deacetylates retinoblastoma (Rb) in the Rb/E2F1 complex, leading to dissociation of E2F1 and enhanced OPC proliferation. Sirt1 knockdown in culture and its targeted ablation in vivo suppresses basal and HX-induced OPC proliferation. Inhibition of Sirt1 also promotes OPC differentiation after HX. Our results indicate that Sirt1 is an essential regulator of OPC proliferation and OL regeneration after neonatal brain injury. Therefore, enhancing Sirt1 activity may promote OL recovery after DWMI.

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“…It has been found that SIRT1 was depleted by free fatty acids and, in turn, SIRT1-dependent deacetylation of mitofusin 2, a protein critical for maintaining mitochondrial integrity and functioning. [ 53 ].…”

Section: Role Of Mitochondrial Dysfunction In Liver Diseasesmentioning

confidence: 99%

Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases

et al. 2018

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In the therapeutic strategies, the role of diet is a well-established factor that can also have an important role in liver diseases. Melatonin, identified in animals, has many antioxidant properties and it was after discovered also in plants, named phytomelatonin. These substances have a positive effect during aging and in pathological conditions too. In particular, it is important to underline that the amount of melatonin produced by pineal gland in human decreases during lifetime and its reduction in blood could be related to pathological conditions in which mitochondria and oxidative stress play a pivotal role. Moreover, it has been indicated that melatonin/phytomelatonin containing foods may provide dietary melatonin, so their ingestion through balanced diets could be sufficient to confer health benefits. In this review, the classification of liver diseases and an overview of the most important aspects of melatonin/phytomelatonin, concerning the differences among their synthesis, their presence in foods and their role in health and diseases, are summarized. The findings suggest that melatonin/phytomelatonin supplementation with diet should be considered important in preventing different disease settings, in particular in liver. Currently, more studies are needed to strengthen the potential beneficial effects of melatonin/phytomelatonin in liver diseases and to better clarify the molecular mechanisms of action.

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Deacetylation of mitofusin-2 by sirtuin-1: A critical event in cell survival after ischemia

Cited by 11 publications

References 10 publications

Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy

Yap regulates gastric cancer survival and migration via SIRT1/Mfn2/mitophagy

Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury

Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases

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