Resveratrol stimulates mitochondrial fusion by a mechanism requiring mitofusin-2

Robb, Ellen L.; Moradi, Fereshteh; Maddalena, Lucas A.; Valente, Andrew; Fonseca, João; Stuart, Jeffrey A.

doi:10.1016/j.bbrc.2017.02.102

Cited by 35 publications

(27 citation statements)

References 30 publications

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“…Several studies have demonstrated that the expression of MNF2 decreased in the kidney, myocardium and retina in diabetes patients, which was associated with excessive apoptosis regulated by BAX/BCL‐2 expression 42, 50, 51. Recently, Robb et al53 have shown that RES stimulates mitochondrial fusion and cell growth through mitofusin activity. Similar to the latter study, we observed an up‐regulation of MNF with a simultaneously decreased FIS expression.…”

Section: Discussionmentioning

confidence: 99%

Combination of resveratrol and 5‐azacytydine improves osteogenesis of metabolic syndrome mesenchymal stem cells

Marycz

Kornicka

Irwin‐Houston³

et al. 2018

J Cellular Molecular Medi

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Endocrine disorders have become more and more frequently diagnosed in humans and animals. In horses, equine metabolic syndrome (EMS) is characterized by insulin resistance, hyperleptinemia, hyperinsulinemia, inflammation and usually by pathological obesity. Due to an increased inflammatory response in the adipose tissue, cytophysiological properties of adipose derived stem cells (ASC) have been impaired, which strongly limits their therapeutic potential. Excessive accumulation of reactive oxygen species, mitochondria deterioration and accelerated ageing of those cells affect their multipotency and restrict the effectiveness of the differentiation process. In the present study, we have treated ASC isolated from EMS individuals with a combination of 5‐azacytydine (AZA) and resveratrol (RES) in order to reverse their aged phenotype and enhance osteogenic differentiation. Using SEM and confocal microscope, cell morphology, matrix mineralization and mitochondrial dynamics were assessed. Furthermore, we investigated the expression of osteogenic‐related genes with RT‐PCR. We also investigated the role of autophagy during differentiation and silenced PARKIN expression with siRNA. Obtained results indicated that AZA/RES significantly enhanced early osteogenesis of ASC derived from EMS animals. Increased matrix mineralization, RUNX‐2, collagen type I and osteopontin levels were noted. Furthermore, we proved that AZA/RES exerts its beneficial effects by modulating autophagy and mitochondrial dynamics through PARKIN and RUNX‐2 activity.

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Section: Discussionmentioning

confidence: 99%

Combination of resveratrol and 5‐azacytydine improves osteogenesis of metabolic syndrome mesenchymal stem cells

Marycz

Kornicka

Irwin‐Houston³

et al. 2018

J Cellular Molecular Medi

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“…Interestingly, we have observed similar results previously (26); rho 0 PC3 cells that are unable to respire also show no growth inhibition by RES. Similarly, mouse embryonic fibroblast cells lacking the mitofusin-2 have compromised respiration and growth that is insensitive to RES (11). Taken together, these observations suggest that RES's growth inhibitory effect in PC3 cells (and perhaps also other cell types) is related to its ability to shift metabolism toward oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 84%

“…The plant polyphenol resveratrol (RES) inhibits cell cycle progression (9) and thus proliferative growth in many cancer cell lines (10). Coincident with these growth inhibitory effects, RES promotes mitochondria network fusion (11), mitochondrial biogenesis, and oxidative phosphorylation (12) in a variety of cancer cell lines. Thus, RES appears to reverse the Warburg effect in many cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol integrates metabolic and growth effects in PC3 prostate cancer cells‑involvement of prolyl hydroxylase and hypoxia inducible factor‑1

et al. 2018

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“…Mitofusin-2 (Mfn2) is one of the most important proteins that accelerates mitochondrial fusion [176]. Resveratrol up-regulates the expression of Mfn2 to stimulate mitochondrial fusion, leading to the decreased viability and proliferation of cancer cells [177]. Triggering mitochondrial fission is another promising strategy in cancer therapy.…”

Section: Resveratrol and Mitochondrial Fusion And Fissionmentioning

confidence: 99%

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

et al. 2020

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Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy.

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Resveratrol stimulates mitochondrial fusion by a mechanism requiring mitofusin-2

Cited by 35 publications

References 30 publications

Combination of resveratrol and 5‐azacytydine improves osteogenesis of metabolic syndrome mesenchymal stem cells

Combination of resveratrol and 5‐azacytydine improves osteogenesis of metabolic syndrome mesenchymal stem cells

Resveratrol integrates metabolic and growth effects in PC3 prostate cancer cells‑involvement of prolyl hydroxylase and hypoxia inducible factor‑1

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

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