Mitochondrial matrix copper complex used in metallation of cytochrome oxidase and superoxide dismutase.
A mitochondrial matrix copper ligand (CuL) complex, conserved in mammalian cells, is the likely source of copper for assembly of cytochrome c oxidase (CcO) and superoxide dismutase 1 (Sod1) within the intermembrane space (IMS) in yeast. Targeting the copper-binding proteins human Sod1 and Crs5 to the mitochondrial matrix results in growth impairment on non-fermentable medium caused by decreased levels of CcO. This effect is reversed by copper supplementation. Matrix-targeted Crs5 diminished Sod1 protein within the IMS and impaired activity of an inner membrane tethered human Sod1. Copper binding by the matrix-targeted proteins attenuates levels of the CuL complex without affecting total mitochondrial copper. These data suggest that attenuation of the matrix CuL complex via heterologous competitors limits available copper for metallation of CcO and Sod1 within the IMS. The ligand also exists in the cytoplasm in an apparent metal-free state.
Cobine
Paul A
PA
University of Utah Health Sciences Center, Departments of Medicine and Biochemistry, Salt Lake City, Utah 84132, USA.
Pierrel
Fabien
F
Bestwick
Megan L
ML
Winge
Dennis R
DR
D001692:Biological Transport; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005816:Genetic Complementation Test; D005990:Glycerol / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008668:Metallothionein / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D018832:Molecular Chaperones; D018384:Oxidative Stress; D010641:Phenotype; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
C089939:CRS5 protein, S cerevisiae; D008024:Ligands; D018832:Molecular Chaperones; C000606290:SOD1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper; D008668:Metallothionein; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003576:Electron Transport Complex IV; D005990:Glycerol