Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action |
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Authors: | Han Wern Lim |
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Affiliation: | Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260, Singapore |
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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, F0F1-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 μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F0F1-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. |
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Keywords: | ANT, adenine nucleotide translocase CATR, carboxyatractyloside CsA, cyclosporin A CUR, curcumin DNP, 2,4-dinitrophenol fccP, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone 6-KCh, 6-ketocholestanol PTP, permeability transition pore |
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