Peyta 2015 Biochim Biophys Acta
|Peyta L, Jarnouen K, Pinault M, Coulouarn C, Guimaraes C, Goupille C, de Barros JP, Chevalier S, Dumas JF, Maillot F, Hatch GM, Loyer P, Servais S (2015) Regulation of hepatic cardiolipin metabolism by TNFα: Implication in cancer cachexia. Biochim Biophys Acta 1851:1490-500.|
Abstract: Cardiolipin (CL) content accumulation leads to an increase in energy wasting in liver mitochondria in a ratmodel of cancer cachexia in which tumor necrosis factor alpha (TNFα) is highly expressed. In this study we investigated the mechanisms involved in liver mitochondria CL accumulation in cancer cachexia and examined if TNFα was involved in this process leading to mitochondrial bioenergetics alterations. We studied gene, protein expression and activity of the main enzymes involved in CL metabolism in liver mitochondria from a rat model of cancer cachexia and in HepaRG hepatocyte-like cells exposed to 20 ng/ml of TNFα for 12 h. Phosphatidylglycerolphosphate synthase (PGPS) gene expression was increased 2.3-fold (p < 0.02) and cardiolipin synthase (CLS) activity decreased 44% (p < 0.03) in cachectic rat livers compared to controls. CL remodeling enzymesmonolysocardiolipin acyltransferase (MLCL AT-1) activity and tafazzin (TAZ) gene expression were increased 30% (p < 0.01) and 50% (p < 0.02), respectively, in cachectic rat livers compared to controls. Incubation of hepatocytes with TNFα increased CL content 15% (p < 0.05), mitochondrial oxygen consumption 33% (p < 0.05), PGPS gene expression 44% (p < 0.05) and MLCL AT-1 activity 20% (p < 0.05) compared to controls. These above findings strongly suggest that in cancer cachexia, TNFα induces a higher energy wasting in liver mitochondria by increasing CL content via upregulation of PGPS expression.
• Keywords: Cardiolipin biosynthesis, Cytokines, Mitochondria, Energy wasting, Liver, Cardiolipin remodeling, Inflammation, HepaRG cells
• O2k-Network Lab: FR Tours Dumas JF
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Pharmacology;toxicology Pathology: Cancer
Organism: Rat Tissue;cell: Liver, Other cell lines Preparation: Intact cells, Permeabilized cells
Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: NS HRR: Oxygraph-2k