Incorporation of marine lipids into mitochondrial membranes increases susceptibility to damage by calcium and reactive oxygen species: evidence for enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty acids.
Experiments were designed to evaluate the susceptibility of mitochondrial membranes enriched with n-3 fatty acids to damage by Ca2+ and reactive oxygen species. Fatty acid content and respiratory function were assessed in renal cortical mitochondria isolated from fish-oil- and beef-tallow-fed rats. Dietary fish oils were readily incorporated into mitochondrial membranes. After exposure to Ca2+ and reactive oxygen species, mitochondria enriched in n-3 fatty acids, and using pyruvate and malate as substrates, had significantly greater changes in state 3 and uncoupled respirations, when compared with mitochondria from rats fed beef tallow. Mitochondrial site 1 (NADH coenzyme Q reductase) activity was reduced to 45 and 85% of control values in fish-oil- and beef-tallow-fed groups, respectively. Exposure to Ca2+ and reactive oxygen species enhance the release of polyunsaturated fatty acids enriched at the sn-2 position of phospholipids from mitochondria of fish-oil-fed rats when compared with similarly treated mitochondria of beef-tallow-fed rats. This release of fatty acids was partially inhibited by dibucaine, the phospholipase A2 inhibitor, which we have previously shown to protect mitochondria against damage associated with Ca2+ and reactive oxygen species. The results indicate that phospholipase A2 is activated in mitochondria exposed to Ca2+ and reactive oxygen species and is responsible, at least in part, for the impairment of respiratory function. Phospholipase A2 activity and mitochondrial damage are enhanced when mitochondrial membranes are enriched with n-3 fatty acids.
Malis
C D
CD
Medical Services, Masschusetts General Hospital, Boston 02114.
Weber
P C
PC
Leaf
A
A
Bonventre
J V
JV
D000818:Animals; D002118:Calcium / Q000633:toxicity*; D004579:Electron Transport; D004789:Enzyme Activation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005395:Fish Oils / Q000378:metabolism*; D007425:Intracellular Membranes / Q000502:physiology; D008293:Malates / Q000378:metabolism; D008563:Membrane Lipids / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D016660:NAD(P)H Dehydrogenase (Quinone); D010100:Oxygen / Q000633:toxicity*; D010101:Oxygen Consumption; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011773:Pyruvates / Q000378:metabolism; D011808:Quinone Reductases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013386:Succinates / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D008293:Malates; D008563:Membrane Lipids; D011773:Pyruvates; D013386:Succinates; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D010741:Phospholipases A; D054467:Phospholipases A2; D010100:Oxygen; D002118:Calcium