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

Schild, Christof; Hahn, Dagmar Karen; Schaller, André; Jackson, Christopher; Rothen-Rutishauser, Barbara; Mirkovitch, Jelena; Nuoffer, Jean-Marc (2014). Mitochondrial leucine tRNA level and PTCD1 are regulated in response to leucine starvation. Amino acids, 46(7), pp. 1775-1783. Springer 10.1007/s00726-014-1730-2

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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 (tRNA(Leu(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, tRNA(Leu(CUN)) and tRNA(Leu(UUR)) as could be shown by RNAi experiments against PTCD1. Therefore, it is likely that decreased PTCD1 protein contributes to the increased tRNA(Leu(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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Endokrinologie / Diabetologie / Metabolik (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Humangenetik

UniBE Contributor:

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

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0939-4451

Publisher:

Springer

Language:

English

Submitter:

André Schaller

Date Deposited:

18 Mar 2015 16:21

Last Modified:

29 Oct 2015 10:17

Publisher DOI:

10.1007/s00726-014-1730-2

PubMed ID:

24710704

BORIS DOI:

10.7892/boris.65306

URI:

https://boris.unibe.ch/id/eprint/65306

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