Hervouet 2006 Biochem Biophys Res Commun

Hervouet E, Pecina P, Demont J, Vojtíšková A, Simonnet H, Houštek J, Godinot C (2006) Inhibition of cytochrome c oxidase subunit 4 precursor processing by the hypoxia mimic cobalt chloride. Biochem Biophys Res Commun 344:1086-93.

Hervouet E, Pecina P, Demont J, Vojtiskova A, Simonnet H, Houstek J, Godinot C (2006) Biochem Biophys Res Commun

Abstract: Cobalt is often used as a hypoxia mimic in cell culture, because it stabilizes the α subunits of the transcription factor, HIF (hypoxia-inducible factor). We have previously shown that HIF stabilization due to a deficiency of the von Hippel Lindau protein (pVHL) in clear cell renal carcinoma (CRCC) was correlated to a down-regulation of oxidative phosphorylation. To better understand this mechanism, we have used CoCl2 in CRCC expressing stably transfected vhl. We show that, in addition to its effect on HIF-α subunits, CoCl2 prevented the normal processing of the precursor of cytochrome c oxidase (COX) subunit 4 and induced COX degradation very likely by inhibiting the mitochondrial intermediate peptidase (MIP) that cleaves the COX4 precursor protein. This cobalt-induced MIP inhibition was however not observed in other human mitochondrial precursor sequences as previously predicted from comparison between human and yeast mitochondrial precursor sequences. • Keywords: Hypoxia-inducible factor, Cytochrome c oxidase subunit 4, Cytochrome c oxidase biogenesis, Mitochondrial precursor processing, Mitochondrial intermediate peptidase, Cobalt chloride, Homo sapiens, Saccharomyces cerevisiae

Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression  Pathology: Cancer 

Organism: Human, Saccharomyces cerevisiae 

Preparation: Intact cells  Enzyme: Complex IV;cytochrome c oxidase  Regulation: Inhibitor  Coupling state: ROUTINE 

HRR: Oxygraph-2k