bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2020‒09‒06
four papers selected by
Gavin McStay
Staffordshire University


  1. Mol Cell. 2020 Aug 04. pii: S1097-2765(20)30515-3. [Epub ahead of print]
    Singh AP, Salvatori R, Aftab W, Aufschnaiter A, Carlström A, Forne I, Imhof A, Ott M.
      Mitochondria contain their own gene expression systems, including membrane-bound ribosomes dedicated to synthesizing a few hydrophobic subunits of the oxidative phosphorylation (OXPHOS) complexes. We used a proximity-dependent biotinylation technique, BioID, coupled with mass spectrometry to delineate in baker's yeast a comprehensive network of factors involved in biogenesis of mitochondrial encoded proteins. This mitochondrial gene expression network (MiGENet) encompasses proteins involved in transcription, RNA processing, translation, or protein biogenesis. Our analyses indicate the spatial organization of these processes, thereby revealing basic mechanistic principles and the proteins populating strategically important sites. For example, newly synthesized proteins are directly handed over to ribosomal tunnel exit-bound factors that mediate membrane insertion, co-factor acquisition, or their mounting into OXPHOS complexes in a special early assembly hub. Collectively, the data reveal the connectivity of mitochondrial gene expression, reflecting a unique tailoring of the mitochondrial gene expression system.
    Keywords:  assembly; co-factor acquisition; gene expression; mitochondria; network; proximity interactions; respiratory chain; ribosome; translation; tunnel exit
    DOI:  https://doi.org/10.1016/j.molcel.2020.07.024
  2. Life (Basel). 2020 Aug 31. pii: E173. [Epub ahead of print]10(9):
    Karakaidos P, Rampias T.
      In eukaryotic cells, mitochondria originated in an α-proteobacterial endosymbiont. Although these organelles harbor their own genome, the large majority of genes, originally encoded in the endosymbiont, were either lost or transferred to the nucleus. As a consequence, mitochondria have become semi-autonomous and most of their processes require the import of nuclear-encoded components to be functional. Therefore, the mitochondrial-specific translation has evolved to be coordinated by mitonuclear interactions to respond to the energetic demands of the cell, acquiring unique and mosaic features. However, mitochondrial-DNA-encoded genes are essential for the assembly of the respiratory chain complexes. Impaired mitochondrial function due to oxidative damage and mutations has been associated with numerous human pathologies, the aging process, and cancer. In this review, we highlight the unique features of mitochondrial protein synthesis and provide a comprehensive insight into the mitonuclear crosstalk and its co-evolution, as well as the vulnerabilities of the animal mitochondrial genome.
    Keywords:  mitochondrial diseases; mitochondrion genetic code; mitonuclear coevolution; mt-DNA repair; translational fidelity
    DOI:  https://doi.org/10.3390/life10090173
  3. J Cell Sci. 2020 Sep 02. pii: jcs.248492. [Epub ahead of print]
    Rawat S, Ghosh S, Mondal D, Anusha V, Raychaudhuri S.
      Proteasome-mediated degradation of misfolded proteins prevents aggregation inside and outside mitochondria. But how do cells safeguard mitochondrial proteome and function despite increased aggregation during proteasome-inactivation? Here, using a novel two-dimensional complexome profiling strategy, we report increased supra-organizations of respiratory complexes (RCs) in proteasome-inhibited cells simultaneous to pelletable aggregation of RC-subunits inside mitochondria. Complex-II (CII) and CV-subunits are increasingly incorporated into oligomers. CI, CIII and CIV-subunits are engaged into supercomplex formation. We unravel unique quinary-states of supercomplexes at early-stress that exhibit plasticity and inequivalence of constituent RCs. Core stoichiometry of CI and CIII is preserved whereas CIV-composition varies. These partially disintegrated supercomplexes remain functionally competent via conformational optimization. Subsequently, increased stepwise integration of RC-subunits into holocomplex and supercomplexes re-establish steady-state stoichiometry. Overall, the mechanism of increased supra-organization of RCs mimics the cooperative unfolding and folding pathways for protein-folding, restricted to RCs only and not observed for any other mitochondrial protein complexes.
    Keywords:  Increased supercomplex; Multistep proteome remodelling; Proteostasis; Quinary supercomplex; Respiratory complex biogenesis; Two-dimensional complexome profiling
    DOI:  https://doi.org/10.1242/jcs.248492
  4. Cell Metab. 2020 Sep 01. pii: S1550-4131(20)30412-5. [Epub ahead of print]32(3): 479-497.e9
    Antonicka H, Lin ZY, Janer A, Aaltonen MJ, Weraarpachai W, Gingras AC, Shoubridge EA.
      We used BioID, a proximity-dependent biotinylation assay with 100 mitochondrial baits from all mitochondrial sub-compartments, to create a high-resolution human mitochondrial proximity interaction network. We identified 1,465 proteins, producing 15,626 unique high-confidence proximity interactions. Of these, 528 proteins were previously annotated as mitochondrial, nearly half of the mitochondrial proteome defined by Mitocarta 2.0. Bait-bait analysis showed a clear separation of mitochondrial compartments, and correlation analysis among preys across all baits allowed us to identify functional clusters involved in diverse mitochondrial functions and to assign uncharacterized proteins to specific modules. We demonstrate that this analysis can assign isoforms of the same mitochondrial protein to different mitochondrial sub-compartments and show that some proteins may have multiple cellular locations. Outer membrane baits showed specific proximity interactions with cytosolic proteins and proteins in other organellar membranes, suggesting specialization of proteins responsible for contact site formation between mitochondria and individual organelles.
    Keywords:  BioID proximity interactions; functional modules; mitochondrial protein proximity map; mitochondrial translation initiation; organellar contact sites; sub-mitochondrial organization
    DOI:  https://doi.org/10.1016/j.cmet.2020.07.017