Myocardial ischemia selectively depletes cardiolipin in rabbit heart subsarcolemmal mitochondria.
Mitochondria contribute to myocyte injury during ischemia. After 30 and 45 min of ischemia in the isolated perfused rabbit heart, subsarcolemmal mitochondria (SSM), located beneath the plasma membrane, sustain a decrease in oxidative phosphorylation through cytochrome oxidase. In contrast, oxidation through cytochrome oxidase in interfibrillar mitochondria (IFM), located between the myofibrils, remains unaffected. Cytochrome oxidase activity in the intact membrane requires an inner mitochondrial membrane lipid environment enriched in cardiolipin. During ischemia, the content of cardiolipin decreased only in SSM, whereas the content of other phospholipids was preserved. Ischemia did not alter the composition of the cardiolipin that remained in SSM. Cardiolipin content was preserved in IFM during ischemia. Thus cardiolipin is a relatively early target of ischemic mitochondrial damage, leading to loss of oxidative phosphorylation through cytochrome oxidase in SSM.
Lesnefsky
E J
EJ
Division of Cardiology, Case Western Reserve University, Cleveland, Ohio 44106, USA. EXL9@po.cwru.edu
Slabe
T J
TJ
Stoll
M S
MS
Minkler
P E
PE
Hoppel
C L
CL
D000818:Animals; D002308:Cardiolipins / Q000032:analysis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003574:Cytochrome c Group / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D008929:Mitochondria, Heart / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D011817:Rabbits; D012508:Sarcolemma / Q000378:metabolism*
D002308:Cardiolipins; D003574:Cytochrome c Group; D010743:Phospholipids