bims-cytox1 2020-10-25 papers

Issue of 2020–10–25
two papers selected by
Gavin McStay, Staffordshire University

Nat Rev Mol Cell Biol. 2020 Oct 22.

Quality control of the mitochondrial proteome.

Jiyao Song, Johannes M Herrmann, Thomas Becker.

Mitochondria contain about 1,000-1,500 proteins that fulfil multiple functions. Mitochondrial proteins originate from two genomes: mitochondrial and nuclear. Hence, proper mitochondrial function requires synchronization of gene expression in the nucleus and in mitochondria and necessitates efficient import of mitochondrial proteins into the organelle from the cytosol. Furthermore, the mitochondrial proteome displays high plasticity to allow the adaptation of mitochondrial function to cellular requirements. Maintenance of this complex and adaptable mitochondrial proteome is challenging, but is of crucial importance to cell function. Defects in mitochondrial proteostasis lead to proteotoxic insults and eventually cell death. Different quality control systems monitor the mitochondrial proteome. The cytosolic ubiquitin-proteasome system controls protein transport across the mitochondrial outer membrane and removes damaged or mislocalized proteins. Concomitantly, a number of mitochondrial chaperones and proteases govern protein folding and degrade damaged proteins inside mitochondria. The quality control factors also regulate processing and turnover of native proteins to control protein import, mitochondrial metabolism, signalling cascades, mitochondrial dynamics and lipid biogenesis, further ensuring proper function of mitochondria. Thus, mitochondrial protein quality control mechanisms are of pivotal importance to integrate mitochondria into the cellular environment.

DOI: https://doi.org/10.1038/s41580-020-00300-2

Mitochondrion. 2020 Oct 15. pii: S1567-7249(20)30200-2. [Epub ahead of print]

Complex IV- the regulatory center of mitochondrial oxidative phosphorylation.

Bernhard Kadenbach.

ATP, the universal energy currency in all living cells, is mainly synthesized in mitochondria by oxidative phosphorylation (OXPHOS). The final and rate limiting step of the respiratory chain is cytochrome c oxidase (COX) which represents the regulatory center of OXPHOS. COX is regulated through binding of various effectors to its ,supernumerary" subunits, by reversible phosphorylation, and by expression of subunit isoforms. Of particular interest is its feedback inhibition by ATP, the final product of OXPHOS. This ,allosteric ATP-inhibition" of phosphorylated and dimeric COX maintains a low and healthy mitochondrial membrane potential (relaxed state), and prevents the formation of ROS (reactive oxygen species) which are known to cause numerous diseases. Excessive work and stress abolish this feedback inhibition of COX by Ca2+-activated dephosphorylation which leads to monomerization and movement of NDUFA4 from complex I to COX with higher rates of COX activity and ATP synthesis (active state) but increased ROS formation and decreased efficiency.

Keywords: ROS; allosteric ATP-inhibition; cytochrome c oxidase; efficiency; membrane potential; oxidative phosphorylation; respiratory control

DOI: https://doi.org/10.1016/j.mito.2020.10.004