Dogan, Sukru Anil ORCID: 0000-0002-1800-2923, Pujol, Claire, Maiti, Priyanka ORCID: 0000-0003-4207-0341, Kukat, Alexandra, Wang, Shuaiyu, Hermans, Steffen, Senft, Katharina, Wibom, Rolf, Rugarli, Elena I. ORCID: 0000-0002-5782-1067 and Trifunovic, Aleksandra (2014). Tissue-Specific Loss of DARS2 Activates Stress Responses Independently of Respiratory Chain Deficiency in the Heart. Cell Metab., 19 (3). S. 458 - 470. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

Full text not available from this repository.

Abstract

Adaptive stress responses activated upon mitochondrial dysfunction are assumed to arise in order to counteract respiratory chain deficiency. Here, we demonstrate that loss of DARS2 (mitochondrial aspartyl-tRNA synthetase) leads to the activation of various stress responses in a tissue-specific manner independently of respiratory chain deficiency. DARS2 depletion in heart and skeletal muscle leads to the severe deregulation of mitochondrial protein synthesis followed by a strong respiratory chain deficit in both tissues, yet the activation of adaptive responses is observed predominantly in cardiomyocytes. We show that the impairment of mitochondrial proteostasis in the heart activates the expression of mitokine FGF21, which acts as a signal for cell-autonomous and systemic metabolic changes. Conversely, skeletal muscle has an intrinsic mechanism relying on the slow turnover of mitochondrial transcripts and higher proteostatic buffering capacity. Our results show that mitochondrial dysfunction is sensed independently of respiratory chain deficiency, questioning the current view on the role of stress responses in mitochondrial diseases.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dogan, Sukru AnilUNSPECIFIEDorcid.org/0000-0002-1800-2923UNSPECIFIED
Pujol, ClaireUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maiti, PriyankaUNSPECIFIEDorcid.org/0000-0003-4207-0341UNSPECIFIED
Kukat, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, ShuaiyuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hermans, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Senft, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wibom, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rugarli, Elena I.UNSPECIFIEDorcid.org/0000-0002-5782-1067UNSPECIFIED
Trifunovic, AleksandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-443587
DOI: 10.1016/j.cmet.2014.02.004
Journal or Publication Title: Cell Metab.
Volume: 19
Number: 3
Page Range: S. 458 - 470
Date: 2014
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MITOCHONDRIAL PROTEIN-SYNTHESIS; GENE-EXPRESSION; MUSCLE; MICE; CARDIOMYOPATHY; MUTATIONS; AUTOPHAGY; MYOPATHY; EMBRYOGENESIS; TRANSCRIPTIONMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/44358

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item