These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Pathogenic variants in glutamyl-tRNAGln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.
    Author: Friederich MW, Timal S, Powell CA, Dallabona C, Kurolap A, Palacios-Zambrano S, Bratkovic D, Derks TGJ, Bick D, Bouman K, Chatfield KC, Damouny-Naoum N, Dishop MK, Falik-Zaccai TC, Fares F, Fedida A, Ferrero I, Gallagher RC, Garesse R, Gilberti M, González C, Gowan K, Habib C, Halligan RK, Kalfon L, Knight K, Lefeber D, Mamblona L, Mandel H, Mory A, Ottoson J, Paperna T, Pruijn GJM, Rebelo-Guiomar PF, Saada A, Sainz B, Salvemini H, Schoots MH, Smeitink JA, Szukszto MJ, Ter Horst HJ, van den Brandt F, van Spronsen FJ, Veltman JA, Wartchow E, Wintjes LT, Zohar Y, Fernández-Moreno MA, Baris HN, Donnini C, Minczuk M, Rodenburg RJ, Van Hove JLK.
    Journal: Nat Commun; 2018 Oct 03; 9(1):4065. PubMed ID: 30283131.
    Abstract:
    Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNAGln). mt-tRNAGln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. Defects involving the mitochondrial protein synthesis machinery cause a broad spectrum of disorders, with often fatal outcome. Here, we describe nine patients from five families with genetic defects in a GatCAB complex subunit, including QRSL1, GATB, and GATC, each showing a lethal metabolic cardiomyopathy syndrome. Functional studies reveal combined respiratory chain enzyme deficiencies and mitochondrial dysfunction. Aminoacylation of mt-tRNAGln and mitochondrial protein translation are deficient in patients' fibroblasts cultured in the absence of glutamine but restore in high glutamine. Lentiviral rescue experiments and modeling in S. cerevisiae homologs confirm pathogenicity. Our study completes a decade of investigations on mitochondrial aminoacylation disorders, starting with DARS2 and ending with the GatCAB complex.
    [Abstract] [Full Text] [Related] [New Search]