Edit Publication: Hervouet 2006 Biochem Biophys Res Commun

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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.
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MiPareas:	Gender Respiration Instruments;methods mt-Biogenesis;mt-density mt-Structure;fission;fusion mt-Membrane mtDNA;mt-genetics nDNA;cell genetics Genetic knockout;overexpression Comparative MiP;environmental MiP Developmental biology Exercise physiology;nutrition;life style mt-Medicine Patients Pharmacology;toxicology mt-Awareness
Pathological states:	COPD Aging;senescence Alzheimer's Autism Cancer Cardiovascular Diabetes Inherited Infectious Myopathy Neurodegenerative Obesity Parkinson's Sepsis Other
Stress conditions:	Hypoxia Cell death Cryopreservation Ischemia-reperfusion Permeability transition Oxidative stress;RONS Temperature Mitochondrial disease
Organism:	Pig Human Mouse Rat Guinea pig Bovines Horse Dog Rabbit Cat Other mammals Chicken Zebrafish Drosophila Artemia Caenorhabditis elegans Saccharomyces cerevisiae Birds Reptiles Amphibians Fishes Chelicerates Crustaceans Hexapods Myriapods Annelids Molluscs Nematodes Other invertebrates Fungi Plants Protists Eubacteria Archea Algae
Tissues;cells:	Fat Heart Skeletal muscle Nervous system Liver Kidney Lung;gill Islet cell;pancreas;thymus Endothelial;epithelial;mesothelial cell Blood cells Genital Other cell lines CHO HEK HeLa Neuroblastoma Fibroblast HUVEC Macrophage-derived Lymphocyte Platelet Stem cells
Preparations:	SMP Intact organism Intact organ Permeabilized cells Permeabilized tissue Homogenate Isolated mitochondria Chloroplasts Enzyme Oxidase;biochemical oxidation Intact cells
Enzyme:	Complex I Adenine nucleotide translocase Complex II;succinate dehydrogenase Complex III Complex IV;cytochrome c oxidase Complex V;ATP synthase Inner mt-membrane transporter Marker enzyme Supercomplex TCA cycle and matrix dehydrogenases Uncoupling protein
Regulation; kinetics:	pH Aerobic glycolysis ADP ATP ATP production AMP Calcium Coupling efficiency;uncoupling Cyt c Flux control Inhibitor Ion;substrate transport mt-Membrane potential Oxygen kinetics PCr;Cr Phosphate Redox state Substrate Temperature Threshold;excess capacity Uncoupler Fatty acid Amino acid Q-junction effect
Coupling:	ET LEAK ROUTINE OXPHOS
Pathways:	F N S Gp DQ CIV NS Other combinations ROX
High-resolution respirometry:	pH Oxygraph-2k TIP2k O2k-Fluorometer NO TPP Ca O2k-Spectrophotometer O2k-Manual O2k-Protocol Theory NextGen-O2k
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