A new type of heme-copper oxidase with alternative electron donors regulated by cytochrome bc1 complex in its supercomplex system

Respiration complex IV (heme-copper oxidase) has been purified from native membranes of the hyperthermophilic eubacterium Aquifex aeolicus. It is a cytochrome ba₃ oxidase and consists of subunit I (coxA2), subunit II (coxB2) and an additional subunit IIa with 5.2 kDa mass. The total mass of complex IV is 85.9 kDa. It oxidizes both cytochrome c and ubiquinol and both reactions are cyanide sensitive. Such a heme-copper oxidase that can switch between two electron donors has never been observed before. The electron donor of this complex IV has been analyzed in its supercomplex system. This supercomplex consists of fully assembled complex III (cytochrome bc₁ complex) and complex IV (heme-copper oxidase). Functional analysis reveals that the electron donor of complex IV is determined by the active states of complex III. Complex IV uses cytochrome c as electron donor when complex III is active, and it uses ubiquinol as electron donor when complex III is inactive (lacking cytochrome c or inhibited by excess ubiquinol).