bims-mitran Biomed News
on Mitochondrial Translation
Issue of 2022‒05‒29
two papers selected by
Andreas Kohler
  1. Identification and Validation of Toxoplasma gondii Mitoribosomal Large Subunit Components.
  2. Defining mitochondrial protein functions through deep multiomic profiling.
  1. Microorganisms. 2022 Apr 21. pii: 863. [Epub ahead of print]10(5):
    Identification and Validation of Toxoplasma gondii Mitoribosomal Large Subunit Components.
    Shikha Shikha, Mariana Ferreira Silva, Lilach Sheiner.
      Mitochondrial ribosomes are fundamental to mitochondrial function, and thus survival, of nearly all eukaryotes. Despite their common ancestry, mitoribosomes have evolved divergent features in different eukaryotic lineages. In apicomplexans, the mitochondrial rRNA is extremely fragmented raising questions about its evolution, protein composition and structure. Apicomplexan mitochondrial translation and the mitoribosomes are essential in all parasites and life stages studied, highlighting mitoribosomes as a promising target for drugs. Still, the apicomplexan mitoribosome is understudied, with one of the obstacles being that its composition is unknown. Here, to facilitate the study of apicomplexan mitoribosomes, we identified and validated components of the mitoribosomal large subunit in the model apicomplexan Toxoplasma gondii.
    Keywords:  LSU; Toxoplasma; apicomplexa; mitochondrion; mitoribosome; parasite; ribosome
    DOI:  https://doi.org/10.3390/microorganisms10050863
  2. Nature. 2022 May 25.
    Defining mitochondrial protein functions through deep multiomic profiling.
    Jarred W Rensvold, Evgenia Shishkova, Yuriy Sverchkov, Ian J Miller, Arda Cetinkaya, Angela Pyle, Mateusz Manicki, Dain R Brademan, Yasemin Alanay, Julian Raiman, Adam Jochem, Paul D Hutchins, Sean R Peters, Vanessa Linke, Katherine A Overmyer, Austin Z Salome, Alexander S Hebert, Catherine E Vincent, Nicholas W Kwiecien, Matthew J P Rush, Michael S Westphall, Mark Craven, Nurten A Akarsu, Robert W Taylor, Joshua J Coon, David J Pagliarini.
      Mitochondria are epicentres of eukaryotic metabolism and bioenergetics. Pioneering efforts in recent decades have established the core protein componentry of these organelles1 and have linked their dysfunction to more than 150 distinct disorders2,3. Still, hundreds of mitochondrial proteins lack clear functions4, and the underlying genetic basis for approximately 40% of mitochondrial disorders remains unresolved5. Here, to establish a more complete functional compendium of human mitochondrial proteins, we profiled more than 200 CRISPR-mediated HAP1 cell knockout lines using mass spectrometry-based multiomics analyses. This effort generated approximately 8.3 million distinct biomolecule measurements, providing a deep survey of the cellular responses to mitochondrial perturbations and laying a foundation for mechanistic investigations into protein function. Guided by these data, we discovered that PIGY upstream open reading frame (PYURF) is an S-adenosylmethionine-dependent methyltransferase chaperone that supports both complex I assembly and coenzyme Q biosynthesis and is disrupted in a previously unresolved multisystemic mitochondrial disorder. We further linked the putative zinc transporter SLC30A9 to mitochondrial ribosomes and OxPhos integrity and established RAB5IF as the second gene harbouring pathogenic variants that cause cerebrofaciothoracic dysplasia. Our data, which can be explored through the interactive online MITOMICS.app resource, suggest biological roles for many other orphan mitochondrial proteins that still lack robust functional characterization and define a rich cell signature of mitochondrial dysfunction that can support the genetic diagnosis of mitochondrial diseases.
    DOI:  https://doi.org/10.1038/s41586-022-04765-3
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