The role of Coa2 in hemylation of yeast Cox1 revealed by its genetic interaction with Cox10.
Saccharomyces cerevisiae cells lacking the cytochrome c oxidase (CcO) assembly factor Coa2 are impaired in Cox1 maturation and exhibit a rapid degradation of newly synthesized Cox1. The respiratory deficiency of coa2 Delta cells is suppressed either by the presence of a mutant allele of the Cox10 farnesyl transferase involved in heme a biosynthesis or through impaired proteolysis by the disruption of the mitochondrial Oma1 protease. Cox10 with an N196K substitution functions as a robust gain-of-function suppressor of the respiratory deficiency of coa2 Delta cells but lacks suppressor activity for two other CcO assembly mutant strains, the coa1 Delta and shy1 Delta mutants. The suppressor activity of N196K mutant Cox10 is dependent on its catalytic function and the presence of Cox15, the second enzyme involved in heme a biosynthesis. Varying the substitution at Asn196 reveals a correlation between the suppressor activity and the stabilization of the high-mass homo-oligomeric Cox10 complex. We postulate that the mutant Cox10 complex has enhanced efficiency in the addition of heme a to Cox1. Coa2 appears to impart stability to the oligomeric wild-type Cox10 complex involved in Cox1 hemylation.
University of Utah Health Sciences Center, Department of Medicine, Salt Lake City, UT 84132, USA.
Megan
M
Bestwick
Oleh
O
Khalimonchuk
Fabien
F
Pierrel
Dennis R
DR
Winge
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D006418:Heme / Q000031:analogs & derivatives* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
C530854:Coa2 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C027728:heme a; D006418:Heme; C526453:Cox1 protein, S cerevisiae; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases; C086105:COX10 protein, S cerevisiae; D045726:Metalloproteases; C480741:Oma1 protein, S cerevisiae