Dosis Facit Sanitatem—Concentration-Dependent Effects of Resveratrol on Mitochondria
1
Institute of Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010 Graz, Austria
2
Department of Dentistry and Maxillofacial Surgery, Medical University of Graz, Billrothgasse 4, 8010 Graz, Austria
*
Author to whom correspondence should be addressed.
Nutrients 2017, 9(10), 1117; https://doi.org/10.3390/nu9101117
Received: 10 August 2017 / Revised: 20 September 2017 / Accepted: 7 October 2017 / Published: 13 October 2017
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
The naturally occurring polyphenol, resveratrol (RSV), is known for a broad range of actions. These include a positive impact on lifespan and health, but also pro-apoptotic anti-cancer properties. Interestingly, cell culture experiments have revealed a strong impact of RSV on mitochondrial function. The compound was demonstrated to affect mitochondrial respiration, structure and mass of mitochondria as well as mitochondrial membrane potential and, ultimately, mitochondria-associated cell death pathways. Notably, the mitochondrial effects of RSV show a very strict and remarkable concentration dependency: At low concentrations, RSV (<50 μM) fosters cellular antioxidant defense mechanisms, activates AMP-activated protein kinase (AMPK)- and sirtuin 1 (SIRT1)-linked pathways and enhances mitochondrial network formation. These mechanisms crucially contribute to the cytoprotective effects of RSV against toxins and disease-related damage, in vitro and in vivo. However, at higher concentrations, RSV (>50 μM) triggers changes in (sub-)cellular Ca2+ homeostasis, disruption of mitochondrial membrane potential and activation of caspases selectively yielding apoptotic cancer cell death, in vitro and in vivo. In this review, we discuss the promising therapeutic potential of RSV, which is most probably related to the compound’s concentration-dependent manipulation of mitochondrial function and structure.
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Keywords:
resveratrol; mitochondria; concentration-dependent effects; cytotoxic agent; cytoprotection
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MDPI and ACS Style
Madreiter-Sokolowski, C.T.; Sokolowski, A.A.; Graier, W.F. Dosis Facit Sanitatem—Concentration-Dependent Effects of Resveratrol on Mitochondria. Nutrients 2017, 9, 1117.
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