Abstract
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.
Highlights
Nature has always been a valuable source for medicine
Since RSV is produced by plants to fight against microbes [1], it seems reasonable that this specific compound strongly affects mitochondria, which are thought to be descendants from ancient bacteria that have been incorporated as an endosymbiont into an ancestor in the modern eukaryotic cell [2,3]
The control of mitochondrial activity is of utmost importance for cellular wellbeing [4] and, obviously for the therapeutic action of RSV, as experiments in mitochondrial DNA deficient Rho 0 cells have revealed functional mitochondria to be crucial for the effects of RSV to occur [5]
Summary
Nature has always been a valuable source for medicine. Notably, many currently-used indispensable drugs were originally developed from plant-derived compounds, such as the antihypertensive agent, verapamil, which is based on papaverine from the opium poppy (Papaver somniferum), or the antidiabetic agent metformin, based on the substance, galegine, from. Driven by the compounds’ beneficial effects on human health, a special interest in polyphenols has occurred. This huge, diverse group of plant metabolites includes well-known compounds, such as the phytoalexin, resveratrol (3,40 ,5-trihydroxy-trans-stilbene; RSV) and the flavonoid, quercetin [2]. The control of mitochondrial activity is of utmost importance for cellular wellbeing [4] and, obviously for the therapeutic action of RSV, as experiments in mitochondrial DNA deficient Rho 0 cells have revealed functional mitochondria to be crucial for the effects of RSV to occur [5]. Experiments revealed a strong concentration-dependent impact of RSV on mitochondrial function, which is of major importance, due to the therapeutic potential of this polyphenol [6–8].
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