Uncoupling of oxidative phosphorylation by curcumin: implication of its cellular mechanism of action

Biochem Biophys Res Commun. 2009 Nov 6;389(1):187-92. doi: 10.1016/j.bbrc.2009.08.121. Epub 2009 Aug 26.

Abstract

Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5'-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F(0)F(1)-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50 microM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F(0)F(1)-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Adolescent
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cell Line, Tumor
  • Curcumin / pharmacology*
  • Humans
  • Male
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / enzymology
  • Oxidative Phosphorylation / drug effects*
  • Proton-Translocating ATPases / metabolism
  • Rats
  • Rats, Wistar
  • Uncoupling Agents / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Antioxidants
  • Uncoupling Agents
  • Adenosine Triphosphate
  • Proton-Translocating ATPases
  • Curcumin