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Mitochondrial leucine tRNA level and PTCD1 are regulated in response to leucine starvation

Schild, Christof ; Hahn, Dagmar ; Schaller, André ; Jackson, Christopher ; Rothen-Rutishauser, Barbara ; Mirkovitch, Jelena ; Nuoffer, Jean-Marc

In: Amino Acids, 2014, vol. 46, no. 7, p. 1775-1783

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    Titre
    • Mitochondrial leucine tRNA level and PTCD1 are regulated in response to leucine starvation
    Auteur
    • Schild, Christof. Institute of Clinical Chemistry, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
    • Hahn, Dagmar. Institute of Clinical Chemistry, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
    • Schaller, André. Division of Human Genetics, Department of Pediatrics, Bern University Hospital and University of Bern, Bern, Switzerland
    • Jackson, Christopher. Institute of Clinical Chemistry, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
    • Rothen-Rutishauser, Barbara. Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland
    • Mirkovitch, Jelena. Institute of Clinical Chemistry, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
    • Nuoffer, Jean-Marc. Institute of Clinical Chemistry, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:325621
    Summary
    Pentatricopeptide repeat domain protein 1 (PTCD1) is a novel human protein that was recently shown to decrease the levels of mitochondrial leucine tRNAs. The physiological role of this regulation, however, remains unclear. Here we show that amino acid starvation by leucine deprivation significantly increased the mRNA steady-state levels of PTCD1 in human hepatocarcinoma (HepG2) cells. Amino acid starvation also increased the mitochondrially encoded leucine tRNA (tRNALeu(CUN)) and the mRNA for the mitochondrial leucyl-tRNA synthetase (LARS2). Despite increased PTCD1 mRNA steady-state levels, amino acid starvation decreased PTCD1 on the protein level. Decreasing PTCD1 protein concentration increases the stability of the mitochondrial leucine tRNAs, tRNALeu(CUN) and tRNALeu(UUR) as could be shown by RNAi experiments against PTCD1. Therefore, it is likely that decreased PTCD1 protein contributes to the increased tRNALeu(CUN) levels in amino acid-starved cells. The stabilisation of the mitochondrial leucine tRNAs and the upregulation of the mitochondrial leucyl-tRNA synthetase LARS2 might play a role in adaptation of mitochondria to amino acid starvation.