Heme Oxigenase-1 is located in liver mitochondria and modulates mitochondrial heme content and metabolism

CONVERSO D, TAILLÉ C, CARRERAS MC, JAITOVICH A, PODEROSO JJ, BOCZKOWSKI J

FASEB JOURNAL

Año: 2006 vol. 20 p. 1236 - 1238

0892-6638

This study investigated whether inducible HO-1 is targeted to mitochondria and its putative effects on oxidative metabolism in rat liver. Western-blot and immune-electron microscopy in whole purified and fractioned organelles showed basal expression of HO-1 protein in both microsomes and mitochondria (inner membrane), accompanied by a parallel HO activity. Inducers of HO-1 increased HO-1 targeting to the inner mitochondrial membrane that also contained biliverdin reductase, supporting both enzymes the same compartmentalization. Induction of mitochondrial HO-1 was associated with a decrease of mitochondrial heme content and selective reduction of protein expression of cytochrome oxidase (COX) subunit I, which is coded by the mitochondrial genome and synthesized in the mitochondria depending on heme availability; these changes resulted in decreased COX spectrum and activity. Mitochondrial HO-1 induction was also associated with down-regulation of mitochondrial-targeted nitric oxide (NO) synthase expression and activity, resulting in a reduction of NO-dependent mitochondrial oxidant yield; inhibition of HO-1 activity reverted these effects. In conclusion, we demonstrated for the first time localization of HO-1 protein in mitochondria. It is surmised that mitochondrial HO-1 has important biological roles in regulating mitochondrial hemeproteins turnover, and in protection against conditions such as hypoxia, neurogenerative diseases or sepsis, in which substantially increased mitochondrial NO and oxidant production have been implicated.