bims-cytox1 2020-10-11 papers

Issue of 2020–10–11
two papers selected by
Gavin McStay, Staffordshire University

World J Biol Chem. 2020 Sep 27. 11(2): 52-61

Regulation of cytochrome c oxidase contributes to health and optimal life.

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 ΔΨm and reactive oxygen species (ROS) formation at low healthy values. Stress signals increase cytosolic calcium leading to Ca2+-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 ΔΨm 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 ΔΨm, high ROS and low efficiency) and complex I (resting state with low ΔΨm, low ROS and high efficiency).

Keywords: Allosteric ATP-inhibition; Cytochrome c oxidase; Dimerization of cytochrome c oxidase; Efficiency of ATP synthesis; NDUFA4; Regulation of respiration; Reversible phosphorylation

DOI: https://doi.org/10.4331/wjbc.v11.i2.52

EMBO Rep. 2020 Oct 05. e51015

Respiratory supercomplexes enhance electron transport by decreasing cytochrome c diffusion distance.

Jens Berndtsson, Andreas Aufschnaiter, Sorbhi Rathore, Lorena Marin-Buera, Hannah Dawitz, Jutta Diessl, Verena Kohler, Antoni Barrientos, Sabrina Büttner, Flavia Fontanesi, Martin Ott.

Respiratory chains are crucial for cellular energy conversion and consist of multi-subunit complexes that can assemble into supercomplexes. These structures have been intensively characterized in various organisms, but their physiological roles remain unclear. Here, we elucidate their function by leveraging a high-resolution structural model of yeast respiratory supercomplexes that allowed us to inhibit supercomplex formation by mutation of key residues in the interaction interface. Analyses of a mutant defective in supercomplex formation, which still contains fully functional individual complexes, show that the lack of supercomplex assembly delays the diffusion of cytochrome c between the separated complexes, thus reducing electron transfer efficiency. Consequently, competitive cellular fitness is severely reduced in the absence of supercomplex formation and can be restored by overexpression of cytochrome c. In sum, our results establish how respiratory supercomplexes increase the efficiency of cellular energy conversion, thereby providing an evolutionary advantage for aerobic organisms.

Keywords: bioenergetics; competitive fitness; cryo-EM; mitochondria; respiratory chain supercomplexes

DOI: https://doi.org/10.15252/embr.202051015