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,andformation 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 todownstreamintermediates.The
CcOassembly 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 coa2∆cells restores respiratory function if Cox10 protein
levels are elevated.TheC-terminalsegmentofCox1is 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 coa2∆ 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 theD336Vmutation 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
