bims-tricox Biomed News
on Translation, ribosomes and COX
Issue of 2025–07–13
four papers selected by
Yash Verma, University of Zurich



  1. Nucleic Acids Res. 2025 Jul 08. pii: gkaf634. [Epub ahead of print]53(13):
      Mitochondrial gene expression needs to be balanced with cytosolic translation to produce oxidative phosphorylation complexes. In yeast, translational feedback loops involving lowly expressed proteins called translational activators help to achieve this balance. Synthesis of cytochrome b (Cytb or COB), a core subunit of complex III in the respiratory chain, is controlled by three translational activators and the assembly factor Cbp3-Cbp6. However, the molecular interface between the COB translational feedback loop and complex III assembly is yet unknown. Here, using protein-proximity mapping combined with selective mitoribosome profiling, we reveal the components and dynamics of the molecular switch controlling COB translation. Specifically, we demonstrate that Mrx4, a previously uncharacterized ligand of the mitoribosomal polypeptide tunnel exit, interacts with either the assembly factor Cbp3-Cbp6 or with the translational activator Cbs2. These reciprocal interactions determine whether the translational activator complex with bound COB messenger RNA (mRNA) can interact with the mRNA channel exit on the small ribosomal subunit for translation initiation. Organization of the feedback loop at the tunnel exit therefore orchestrates mitochondrial translation with respiratory chain biogenesis.
    DOI:  https://doi.org/10.1093/nar/gkaf634
  2. J Cell Sci. 2025 Jul 01. pii: jcs263701. [Epub ahead of print]138(13):
      Most mitochondrial proteins are imported through the actions of the presequence translocase of the inner membrane, the TIM23 complex, which requires energy in the form of the electrochemical potential of the inner membrane and ATP. Conversions of energy in mitochondria are disturbed in mitochondrial disorders that affect oxidative phosphorylation. Despite the widely accepted dependence of protein import into mitochondria on mitochondrial bioenergetics, effects of mitochondrial disorders on biogenesis of the mitochondrial proteome are poorly characterized. Here, we describe molecular tools that can be used to explore mitochondrial protein import in intact cells, the mitoRUSH assay, and a novel method based on labeling of nascent proteins with an amino acid analog and click chemistry. Using these orthogonal approaches, we discovered that defects in the electron transport chain and manipulating the expression of TIMM23, as well as the TIMM17A or TIMM17B paralogs, in human cells are associated with a decrease in protein import into mitochondria. We postulate that in the absence of a functional electron transfer chain, the mechanisms that support electrochemical potential of the inner membrane and ATP production are insufficient to sustain the import of proteins to mitochondria.
    Keywords:  Bioenergetics; Mitochondria; Mitochondrial diseases; Protein import; TIM23; Translocase; mitoRUSH
    DOI:  https://doi.org/10.1242/jcs.263701
  3. PLoS Genet. 2025 Jul 07. 21(7): e1011773
      Mitochondria perform essential metabolic functions and respond rapidly to changes in metabolic and stress conditions. As the majority of mitochondrial proteins are nuclear-encoded, intricate post-transcriptional regulation is crucial to enable mitochondria to adapt to changing cellular demands. The eukaryotic Clustered mitochondria protein family has emerged as an important regulator of mitochondrial function during metabolic shifts. Here, we show that the Drosophila melanogaster and Saccharomyces cerevisiae Clu/Clu1 proteins form dynamic, membraneless, mRNA-containing granules adjacent to mitochondria in response to metabolic changes. Yeast Clu1 regulates the translation of a subset of nuclear-encoded mitochondrial proteins by interacting with their mRNAs while these are engaged in translation. We further show that Clu1 regulates translation by interacting with polysomes, independently of whether it is in a diffuse or granular state. Our results demonstrate remarkable functional conservation with other members of the Clustered mitochondria protein family and suggest that Clu/Clu1 granules isolate and concentrate ribosomes engaged in translating their mRNA targets, thus, integrating metabolic signals with the regulation of mitochondrial protein synthesis.
    DOI:  https://doi.org/10.1371/journal.pgen.1011773