bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2021‒09‒19
two papers selected by
Gavin McStay
Staffordshire University

  1. Biophys Physicobiol. 2021 ;18 186-195
      Cytochrome c oxidase (CcO), a terminal oxidase in the respiratory chain, catalyzes the reduction of O2 to water coupled with the proton pump across the membrane. Mitochondrial CcO exists in monomeric and dimeric forms, and as a monomer as part of the respiratory supercomplex, although the enzymatic reaction proceeds in the CcO monomer. Recent biochemical and crystallographic studies of monomeric and dimeric CcOs have revealed functional and structural differences among them. In solubilized mitochondrial membrane, the monomeric form is dominant, and a small amount of dimer is observed. The activity of the monomeric CcO is higher than that of the dimer, suggesting that the monomer is the active form. In the structure of monomeric CcO, a hydrogen bond network of water molecules is formed at the entrance of the proton transfer K-pathway, and in dimeric CcO, this network is altered by a cholate molecule binding between monomers. The specific binding of the cholate molecule at the dimer interface suggests that the binding of physiological ligands similar in size or shape to cholate could also trigger dimer formation as a physiological standby form. Because the dimer interface also contains weak interactions of nonspecifically bound lipid molecules, hydrophobic interactions between the transmembrane helices, and a Met-Met interaction between the extramembrane regions, these interactions could support the stabilization of the standby form. Structural analyses also suggest that hydrophobic interactions of cardiolipins bound to the trans-membrane surface of CcO are involved in forming the supercomplex.
    Keywords:  cholate; complex IV; lipid; mitochondria; respiratory chain
  2. Redox Biol. 2021 Sep 10. pii: S2213-2317(21)00284-6. [Epub ahead of print]46 102125
      Heme is an essential cofactor required for a plethora of cellular processes in eukaryotes. In metazoans the heme biosynthetic pathway is typically partitioned between the cytosol and mitochondria, with the first and final steps taking place in the mitochondrion. The pathway has been extensively studied and its biosynthetic enzymes structurally characterized to varying extents. Nevertheless, understanding of the regulation of heme synthesis and factors that influence this process in metazoans remains incomplete. Therefore, we investigated the molecular organization as well as the physical and genetic interactions of the terminal pathway enzyme, ferrochelatase (Hem15), in the yeast Saccharomyces cerevisiae. Biochemical and genetic analyses revealed dynamic association of Hem15 with Mic60, a core component of the mitochondrial contact site and cristae organizing system (MICOS). Loss of MICOS negatively impacts Hem15 activity, affects the size of the Hem15 high-mass complex, and results in accumulation of reactive and potentially toxic tetrapyrrole precursors that may cause oxidative damage. Restoring intermembrane connectivity in MICOS-deficient cells mitigates these cytotoxic effects. These data provide new insights into how heme biosynthetic machinery is organized and regulated, linking mitochondrial architecture-organizing factors to heme homeostasis.
    Keywords:  Ferrochelatase; Heme; MICOS; Mitochondria; Yeast