Open AccessRegulation of cytochrome c oxidase contributes to health and optimal life
Author(s) -
Bernhard Kadenbach
Publication year - 2020
Publication title -
world journal of biological chemistry
Language(s) - English
Resource type - Journals
ISSN - 1949-8454
DOI - 10.4331/wjbc.v11.i2.52
Subject(s) - allosteric regulation , dephosphorylation , mitochondrion , oxidative phosphorylation , cytosol , cytochrome c oxidase , reactive oxygen species , chemistry , protein subunit , inner mitochondrial membrane , biophysics , biochemistry , oxidase test , microbiology and biotechnology , oxidative stress , phosphorylation , biology , enzyme , phosphatase , gene
The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation. Cytochrome c oxidase (CytOx), the oxygen accepting and rate-limiting step of the respiratory chain, regulates the supply of variable ATP demands in cells by "allosteric ATP-inhibition of CytOx." This mechanism is based on inhibition of oxygen uptake of CytOx at high ATP/ADP ratios and low ferrocytochrome c concentrations in the mitochondrial matrix via cooperative interaction of the two substrate binding sites in dimeric CytOx. The mechanism keeps mitochondrial membrane potential ΔΨ m and reactive oxygen species (ROS) formation at low healthy values. Stress signals increase cytosolic calcium leading to Ca 2+ -dependent dephosphorylation of CytOx subunit I at the cytosolic side accompanied by switching off the allosteric ATP-inhibition and monomerization of CytOx. This is followed by increase of ΔΨ m and formation of ROS. A hypothesis is presented suggesting a dynamic change of binding of NDUFA4, originally identified as a subunit of complex I, between monomeric CytOx (active state with high ΔΨ m , high ROS and low efficiency) and complex I (resting state with low ΔΨ m , low ROS and high efficiency).