Effect of resveratrol on mitochondrial function: implications in parkin-associated familiar Parkinson's disease

Biochim Biophys Acta. 2014 Jul;1842(7):902-15. doi: 10.1016/j.bbadis.2014.02.010. Epub 2014 Feb 25.


Mitochondrial dysfunction and oxidative stress occur in Parkinson's disease (PD), but the molecular mechanisms controlling these events are not completely understood. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a transcriptional coactivator known as master regulator of mitochondrial functions and oxidative metabolism. Recent studies, including one from our group, have highlighted altered PGC-1α activity and transcriptional deregulation of its target genes in PD pathogenesis suggesting it as a new potential therapeutic target. Resveratrol, a natural polyphenolic compound proved to improve mitochondrial activity through the activation of several metabolic sensors resulting in PGC-1α activation. Here we have tested in vitro the effect of resveratrol treatment on primary fibroblast cultures from two patients with early-onset PD linked to different Park2 mutations. We show that resveratrol regulates energy homeostasis through activation of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) and raise of mRNA expression of a number of PGC-1α's target genes resulting in enhanced mitochondrial oxidative function, likely related to a decrease of oxidative stress and to an increase of mitochondrial biogenesis. The functional impact of resveratrol treatment encompassed an increase of complex I and citrate synthase activities, basal oxygen consumption, and mitochondrial ATP production and a decrease in lactate content, thus supporting a switch from glycolytic to oxidative metabolism. Moreover, resveratrol treatment caused an enhanced macro-autophagic flux through activation of an LC3-independent pathway. Our results, obtained in early-onset PD fibroblasts, suggest that resveratrol may have potential clinical application in selected cases of PD-affected patients.

Keywords: Mitochondria; PGC-1α; Parkin; Parkinson's disease; Resveratrol; Sirtuin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Adenosine Triphosphate / genetics
  • Adenosine Triphosphate / metabolism
  • Cells, Cultured
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Mitochondria / drug effects*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • NAD / genetics
  • NAD / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Oxygen Consumption / drug effects
  • Oxygen Consumption / genetics
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Resveratrol
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Stilbenes / pharmacology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism*


  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Stilbenes
  • Transcription Factors
  • NAD
  • Adenosine Triphosphate
  • Ubiquitin-Protein Ligases
  • parkin protein
  • AMP-Activated Protein Kinases
  • SIRT1 protein, human
  • Sirtuin 1
  • Resveratrol