Mitochondrial heme-oxygenase-1 contributes to mtNOS degradation

CONVERSO D; TAILLÉ C; FRANCO MC; CARRERAS MC; BOCZKOWSKI J; PODEROSO JJ

Seattle, EEUU

Congreso; X Annual Meeting of the Society for Free Radical Biology and Medicine; 2003

Society for Free Radical Biology and Medicine

Heme-oxygenases (HO) comprises a group of enzyme isoforms catalyzing heme degradation to biliverdin and CO. Moreover, the enzymes act on the transcriptional regulation of different genes and possess antioxidant properties as well. HO-1 is found in liver, spleen, and erythropoietic tissue and can be induced by heme itself and other metalloporphyrins, hormones, starvation, stress, toxins, and xenobiotics. HO-1 is present in microsomes but considering the modulation of different hemeproteins, we attempted to search a putative enzyme localization and function in purified rat liver mitochondria. Mitochondrial and microsomal HO-1 expression and activities were analyzed by immunoblotting, immune-electron microscopy and bilirubin production in controls, after administration of 50 mg/Kg hemin or 50 mmol/Kg protoporphyrin IX (SnPP IX, HO inhibitor). HO-1 was presen  in microsomes and mitochondrias and hemin clearly induced protein expression in both fractions (about +120% in mitochondria); SnPP IX provoked a low inhibition of HO-1, we analyzed expression and activity of mtNOS in the same conditions. In accord to hemin-induced mtHO-1, mtNOS expression and activity markedly decreased by 50%. In line with low matrix NO, mitochondria from hemin-treated rats had higher O2 uptake than controls. Moreover, administration of T3, a known HO-1 inducer, increased the enzyme and mitochondrial O2 uptake while markedly decreased mtNOS activity and expression. The data suggest that HO-1 is translocated to mitochondria where it contributes to hormonal regulation and catabolism of hemeproteins resulting in differential organelle modulation.