Succinimidyl oleate, established inhibitor of CD36/FAT translocase inhibits complex III of mitochondrial respiratory chain.
The functional role of CD36 protein detected in mitochondrial fractions in long chain fatty acid (LCFA) oxidation is unclear due to conflicting results obtained in Cd36 knockout mice and experiments using sulfo-N-succinimidyl oleate (SSO) for inhibition of CD36 mediated LCFA transport. We investigated effect of SSO on mitochondrial respiration and found that SSO substantially inhibits not only LCFA oxidation, but also oxidation of flavoprotein- and NADH-dependent substrates and generation of mitochondrial membrane potential. Experiments in rat liver, heart and kidney mitochondria demonstrated a direct effect on mitochondrial respiratory chain with the most pronounced inhibition of the complex III (IC(50) 4microM SSO). The results presented here show that SSO is a potent and irreversible inhibitor of mitochondrial respiratory chain.
Drahota
Zdenek
Z
Institute of Physiology and Center for Applied Genomics, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague, Czech Republic.
Vrbacký
Marek
M
Nůsková
Hana
H
Kazdová
Ludmila
L
Zídek
Václav
V
Landa
Vladimír
V
Pravenec
Michal
M
Houstek
Josef
J
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018955:CD36 Antigens / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors*; D005227:Fatty Acids / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D009829:Oleic Acids / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D013388:Succinimides / Q000494:pharmacology*
D018955:CD36 Antigens; D005227:Fatty Acids; D009829:Oleic Acids; D013388:Succinimides; C120556:sulfo-N-succinimidyl oleate; D014450:Electron Transport Complex III