Oxidation of cardiolipin is involved in functional impairment and disintegration of liver mitochondria by hypoxia/reoxygenation in the presence of increased Ca²⁺ concentrations.
The aim of this study was to investigate the interrelationship between the mitochondrial phospholipid cardiolipin (CL), mitochondrial respiration and morphology in dependence on hypoxia/reoxygenation and Ca(2+). Therefore, we subjected rat liver mitochondria to hypoxia/reoxygenation at different extramitochondrial Ca(2+) concentrations and analysed mitochondrial respiration, morphology, CL content, the composition of molecular CL species, oxidation of CL and two mono-lyso-CL species. Hypoxia/reoxygenation in the presence of elevated extramitochondrial Ca(2+) concentration caused dramatic impairment of mitochondrial respiration and morphology. Concomitantly, increased amounts of oxidised CL were detected in the incubation medium after the treatment. Hypoxia/reoxygenation alone caused degradation of CL. The treatments had no effect on the composition of molecular CL species. Our data support the hypothesis that CL oxidation and CL degradation are involved in mitochondrial injury caused by hypoxia/reoxygenation and Ca(2+). Our results further suggest that prevention of CL oxidation by modification of CL composition may support the beneficial action of antioxidants during hypoxia/reoxygenation in the presence of elevated Ca(2+) concentrations.
Department of Pathological Biochemistry, Medical Faculty, Otto-von-Guericke-University, Leipziger Str. 44, 39120, Magdeburg, Germany.
Jan-Christian
JC
Martens
Gerburg
G
Keilhoff
Andreas
A
Gardemann
Lorenz
L
Schild
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002308:Cardiolipins / Q000378:metabolism*; D019069:Cell Respiration; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D002308:Cardiolipins; D002118:Calcium