title: Efficiency of oxidative phosphorylation in liver mitochondria is decreased in a rat model of peritoneal carcinosis.
abstract: OBJECTIVE
  Cancer cachexia is a dynamic process characterized by a negative energy balance induced by anorexia and hypermetabolism. The mechanisms leading to hypermetabolism are not totally elucidated. This study examines the efficiency of oxidative phosphorylation and energy wasting in liver mitochondria isolated from rats with cancer cachexia induced by peritoneal carcinosis (PC).
  
  
  METHODS
  PC was generated by an intraperitoneal injection of cancer cells (PROb) in BDIX rats. The efficiency of oxidative phosphorylation and energy wasting as well as the role played by reactive oxygen species (ROS) and cardiolipin (mitochondrial inner membrane phospholipid) in these processes were assessed in liver mitochondria of PC and pair-fed control rats.
  
  
  RESULTS
  The efficiency of oxidative phosphorylation decreased (-26%) while energy wasting increased (+22%) in liver mitochondria from PC compared to control rats. The increased energy wasting was associated with a higher cardiolipin content (+55%, p<0.05; R(2)=0.64, p<0.05) and with a lower n-6/n-3 polyunsaturated fatty acid ratio in cardiolipin (-45%, p<0.05; R(2)=0.21, p<0.05) in PC rats. ROS production was increased by 12-fold in liver mitochondria from PC rats.
  
  
  CONCLUSIONS
  The efficiency of ATP synthesis was reduced and energy wasting processes were increased in liver mitochondria of PC rats. This suggests that liver mitochondria from PC rats request more nutrients than liver mitochondria from control rats to maintain the same ATP production. These alterations were associated to the content and fatty acid composition of cardiolipin.
authors.affiliation: INSERM U921, Nutrition, Croissance et Cancer, F-37032 Tours, France. jean-francois.dumas@univ-tours.fr
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dumas
authors.forename: Caroline
authors.initials: C
authors.lastname: Goupille
authors.forename: Cloé Mimsy
authors.initials: CM
authors.lastname: Julienne
authors.forename: Michelle
authors.initials: M
authors.lastname: Pinault
authors.forename: Stéphan
authors.initials: S
authors.lastname: Chevalier
authors.forename: Philippe
authors.initials: P
authors.lastname: Bougnoux
authors.forename: Stéphane
authors.initials: S
authors.lastname: Servais
authors.forename: Charles
authors.initials: C
authors.lastname: Couet
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002100:Cachexia / Q000378:metabolism; D002308:Cardiolipins / Q000032:analysis; D045744:Cell Line, Tumor; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010101:Oxygen Consumption; D010534:Peritoneal Neoplasms / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002308:Cardiolipins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate