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 TNFΞ±: Implication in cancer cachexia. Biochim Biophys Acta 1851:1490-500. |
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) Biochim Biophys Acta
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 (TNFΞ±) is highly expressed. In this study we investigated the mechanisms involved in liver mitochondria CL accumulation in cancer cachexia and examined if TNFΞ± 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 TNFΞ± 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 TNFΞ± 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, TNFΞ± induces a higher energy wasting in liver mitochondria by increasing CL content via upregulation of PGPS expression. β’ Keywords: Cardiolipin biosynthesis, Cytokines, Mitochondria, Energy wasting, Liver, Cardiolipin remodeling, Inflammation, HepaRG cells
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
