Oligomerization of heme o synthase in cytochrome oxidase biogenesis is mediated by cytochrome oxidase assembly factor Coa2.
The synthesis of the heme a cofactor used in cytochrome c oxidase (CcO) is dependent on the sequential action of heme o synthase (Cox10) and heme a synthase (Cox15). The active state of Cox10 appears to be a homo-oligomeric complex, and formation of this complex is dependent on the newly synthesized CcO subunit Cox1 and the presence of an early Cox1 assembly intermediate. Cox10 multimerization is triggered by progression of Cox1 from the early assembly intermediate to downstream intermediates. The CcO assembly factor Coa2 appears important in coupling the presence of newly synthesized Cox1 to Cox10 oligomerization. Cells lacking Coa2 are impaired in Cox10 complex formation as well as the formation of a high mass Cox15 complex. Increasing Cox1 synthesis in coa2Δ cells restores respiratory function if Cox10 protein levels are elevated. The C-terminal segment of Cox1 is important in triggering Cox10 oligomerization. Expression of the C-terminal 54 residues of Cox1 appended to a heterologous matrix protein leads to efficient Cox10 complex formation in coa2Δ cells, but it fails to induce Cox15 complex formation. The state of Cox10 was evaluated in mutants, which predispose human patients to CcO deficiency and the neurological disorder Leigh syndrome. The presence of the D336V mutation in the yeast Cox10 backbone results in a catalytically inactive enzyme that is fully competent to oligomerize. Thus, Cox10 oligomerization and catalytic activation are separate processes and can be uncoupled.
Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Oleh
O
Khalimonchuk
Hyung
H
Kim
Talina
T
Watts
Xochitl
X
Perez-Martinez
Dennis R
DR
Winge
D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D001483:Base Sequence; D001704:Biopolymers / Q000378:metabolism*; D017931:DNA Primers; D003576:Electron Transport Complex IV / Q000096:biosynthesis / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D001704:Biopolymers; C530854:Coa2 protein, S cerevisiae; D017931:DNA Primers; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases; C086105:COX10 protein, S cerevisiae