bims-resufa 2021-01-17 papers

Issue of 2021‒01‒17
two papers selected by
Vera Strogolova
Strong Microbials, Inc

Mol Cell Proteomics. 2020 Jul;pii: S1535-9476(20)34978-1. [Epub ahead of print]19(7): 1145-1160

HIGD2A is Required for Assembly of the COX3 Module of Human Mitochondrial Complex IV.

Daniella H Hock, Boris Reljic, Ching-Seng Ang, Linden Muellner-Wong, Hayley S Mountford, Alison G Compton, Michael T Ryan, David R Thorburn, David A Stroud.

Assembly factors play a critical role in the biogenesis of mitochondrial respiratory chain complexes I-IV where they assist in the membrane insertion of subunits, attachment of co-factors, and stabilization of assembly intermediates. The major fraction of complexes I, III and IV are present together in large molecular structures known as respiratory chain supercomplexes. Several assembly factors have been proposed as required for supercomplex assembly, including the hypoxia inducible gene 1 domain family member HIGD2A. Using gene-edited human cell lines and extensive steady state, translation and affinity enrichment proteomics techniques we show that loss of HIGD2A leads to defects in the de novo biogenesis of mtDNA-encoded COX3, subsequent accumulation of complex IV intermediates and turnover of COX3 partner proteins. Deletion of HIGD2A also leads to defective complex IV activity. The impact of HIGD2A loss on complex IV was not altered by growth under hypoxic conditions, consistent with its role being in basal complex IV assembly. Although in the absence of HIGD2A we show that mitochondria do contain an altered supercomplex assembly, we demonstrate it to harbor a crippled complex IV lacking COX3. Our results redefine HIGD2A as a classical assembly factor required for building the COX3 module of complex IV.

Keywords: Mitochondria function or biology; OXPHOS; cytochrome c oxidase; energy metabolism; knockouts; mitochondria; mitochondrial disease; mtDNA translation; respirasome; translation

DOI: https://doi.org/10.1074/mcp.RA120.002076

J Exp Biol. 2021 Jan 12. pii: jeb.237156. [Epub ahead of print]

Effects of variable oxygen regimes on mitochondrial bioenergetics and reactive oxygen species production in a marine bivalve Mya arenaria.

Natascha Ouillon, Eugene P Sokolov, Stefan Otto, Gregor Rehder, Inna M Sokolova.

Estuarine and coastal benthic organisms often experience fluctuations in oxygen levels that can negatively impact their mitochondrial function and aerobic metabolism. To study these impacts, we exposed a common sediment-dwelling bivalve, the soft-shell clam Mya arenaria, for 21 days to chronic hypoxia (PO2∼4.1 kPa), cyclic hypoxia (PO2∼12.7-1.9 kPa, mean=5.7 kPa), or normoxia (PO2∼21.1 kPa). pH was manipulated to mimic the covariation in CO2/pH and oxygen levels in coastal hypoxic zones. Mitochondrial respiration, including the proton leak, the capacity for oxidative phosphorylation (OXPHOS), the maximum activity of the electron transport system (ETS), reactive oxygen species (ROS) production, and activity and oxygen affinity of cytochrome c oxidase (CCO) were assessed. Acclimation to constant hypoxia did not affect the studied mitochondrial traits except for a modest decrease in the OXPHOS coupling efficiency. Cyclic hypoxia had no effect on the OXPHOS or ETS capacity, but increased the proton leak and lowered the mitochondrial OXPHOS coupling efficiency. Furthermore, mitochondria of clams acclimated to cyclic hypoxia had higher rates of ROS generation compared with the clams acclimated to normoxia or chronic hypoxia. CCO activity was upregulated under the cyclic hypoxia, but oxygen affinity of CCO did not change. These findings indicate that long-term cyclic hypoxia has a stronger impact on the mitochondria of M. arenaria than chronic hypoxia and might lead to impaired ATP synthesis, higher costs of the mitochondrial maintenance and oxidative stress. These changes might negatively affect populations of M. arenaria in the coastal Baltic Sea under increasing hypoxia pressure.

Keywords: Bivalve; Chronic hypoxia; Cyclic hypoxia; Electron leak; Mitochondrial proton leak; Oxidative phosphorylation; Oxidative stress

DOI: https://doi.org/10.1242/jeb.237156