title: Cardiolipin content is involved in liver mitochondrial energy wasting associated with cancer-induced cachexia without the involvement of adenine nucleotide translocase.
abstract: Cancer-induced cachexia describes the progressive skeletal muscle wasting associated with many cancers leading to shortened survival time in cancer patients. We previously reported that cardiolipin content and energy-wasting processes were both increased in liver mitochondria in a rat model of peritoneal carcinosis (PC)-induced cachexia. To increase the understanding of the cellular biology of cancer cachexia, we investigated the involvement of adenine nucleotide translocator (ANT) in mitochondrial energy-wasting processes in liver mitochondria of PC and pair-fed control rats and its interactions with cardiolipin in isolated liver mitochondria from healthy rats exposed to cardiolipin-enriched liposomes. We showed in this study that functional ANT content was decreased in liver mitochondria from PC rats but without any effects on the efficiency of ATP synthesis. Moreover, non-phosphorylating energy wasting was not affected by saturating concentrations of carboxyatractylate (CAT), a potent inhibitor of ANT, in liver mitochondria from PC rats. Decreased efficiency of ATP synthesis was found in normal liver mitochondria exposed to cardiolipin-enriched liposomes, with increased non-phosphorylating energy wasting, thus mimicking mitochondria from PC rats. However, the functional ANT content in these cardiolipin-enriched mitochondria was unchanged, although non-phosphorylating energy wasting was reduced by CAT-induced inhibition of ANT. Finally, non-phosphorylating energy wasting was increased in cardiolipin-enriched mitochondria with substrates for complexes 1 and 2, but not for complex 4. In conclusion, increased energy wasting measured in liver mitochondria from rats with cancer cachexia is dependent on cardiolipin but independent of ANT. Interactions between ANT and cardiolipin are modified when cancer cachexia occurs.
authors.affiliation: INSERM UMR1069, "Nutrition, Growth and Cancer", F-37032 Tours, France.
authors.forename: Cloé Mimsy
authors.initials: CM
authors.lastname: Julienne
authors.affiliation: INSERM UMR1069, "Nutrition, Growth and Cancer", F-37032 Tours, France; CHRU Bretonneau, F-37044 Tours, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Tardieu
authors.affiliation: INSERM UMR1069, "Nutrition, Growth and Cancer", F-37032 Tours, France; Université François-Rabelais, F-37032 Tours, France.
authors.forename: Stéphan
authors.initials: S
authors.lastname: Chevalier
authors.affiliation: INSERM UMR1069, "Nutrition, Growth and Cancer", F-37032 Tours, France; Université François-Rabelais, F-37032 Tours, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Pinault
authors.affiliation: INSERM UMR1069, "Nutrition, Growth and Cancer", F-37032 Tours, France; Université François-Rabelais, F-37032 Tours, France; CHRU Bretonneau, F-37044 Tours, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bougnoux
authors.affiliation: INSERM UMR1069, "Nutrition, Growth and Cancer", F-37032 Tours, France; Université François-Rabelais, F-37032 Tours, France; CHRU Bretonneau, F-37044 Tours, France.
authors.forename: François
authors.initials: F
authors.lastname: Labarthe
authors.affiliation: INSERM UMR1069, "Nutrition, Growth and Cancer", F-37032 Tours, France; Université François-Rabelais, F-37032 Tours, France; CHRU Bretonneau, F-37044 Tours, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Couet
authors.affiliation: INSERM UMR1069, "Nutrition, Growth and Cancer", F-37032 Tours, France; Université François-Rabelais, F-37032 Tours, France; IUT, F-37044 Tours, France. Electronic address: stephane.servais@univ-tours.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Servais
authors.affiliation: INSERM UMR1069, "Nutrition, Growth and Cancer", F-37032 Tours, France; Université François-Rabelais, F-37032 Tours, France. Electronic address: jean-francois.dumas@univ-tours.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dumas
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002100:Cachexia / Q000150:complications / Q000378:metabolism*; D002308:Cardiolipins / Q000378:metabolism*; D004195:Disease Models, Animal; D004734:Energy Metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000150:complications / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
chemical_list: D002308:Cardiolipins; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases
keywords: ANT; ATP synthesis; Cardiolipin; Oxidative phosphorylation; Peritoneal carcinosis; Undernutrition