Redox regulation of SCO protein function: controlling copper at a mitochondrial crossroad.
Reversible changes in the redox state of cysteine residues represent an important mechanism with which to regulate protein function. In mitochondria, such redox reactions modulate the localization or activity of a group of proteins, most of which function in poorly defined pathways with essential roles in copper delivery to cytochrome c oxidase (COX) during holoenzyme biogenesis. To date, a total of 8 soluble (COX17, COX19, COX23, PET191, CMC1-4) and 3 integral membrane (COX11, SCO1, SCO2) accessory proteins with cysteine-containing domains that reside within the mitochondrial intermembrane space (IMS) have been identified in yeast, all of which have human orthologues. Compelling evidence from studies of COX17, SCO1, and SCO2 argues that regulation of the redox state of their cysteines is integral to their metallochaperone function. Redox also appears to be crucial to the regulation of a SCO-dependent, mitochondrial signaling pathway that modulates the rate of copper efflux from the cell. Here, I review our understanding of redox-dependent modulation of copper delivery to COX and IMS-localized copper-zinc superoxide dismutase (SOD1) during the maturation of each enzyme, and discuss how this in turn may serve to functionally couple mitochondrial copper handling pathways with those localized elsewhere in the cell to regulate cellular copper homeostasis.
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada. scot.leary@usask.ca
Scot C
SC
Leary
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism*; D003300:Copper / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015003:Yeasts / Q000378:metabolism
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D003300:Copper; D003576:Electron Transport Complex IV; D003545:Cysteine