Segref, Alexandra, Kevei, Eva ORCID: 0000-0002-0560-9208, Pokrzywa, Wojciech ORCID: 0000-0002-5110-4462, Schmeisser, Kathrin, Mansfeld, Johannes, Livnat-Levanon, Nurit, Ensenauer, Regina, Glickman, Michael H., Ristow, Michael ORCID: 0000-0003-2109-2453 and Hoppe, Thorsten ORCID: 0000-0002-4734-9352 (2014). Pathogenesis of Human Mitochondrial Diseases Is Modulated by Reduced Activity of the Ubiquitin/Proteasome System. Cell Metab., 19 (4). S. 642 - 653. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

Full text not available from this repository.

Abstract

Mitochondria maintain cellular homeostasis by coordinating ATP synthesis with metabolic activity, redox signaling, and apoptosis. Excessive levels of mitochondria-derived reactive oxygen species (ROS) promote mitochondrial dysfunction, triggering numerous metabolic disorders. However, the molecular basis for the harmful effects of excessive ROS formation is largely unknown. Here, we identify a link between mitochondrial stress and ubiquitin-dependent proteolysis, which supports cellular surveillance both in Caenorhabditis elegans and humans. Worms defective in respiration with elevated ROS levels are limited in turnover of a GFP-based substrate protein, demonstrating that mitochondrial stress affects the ubiquitin/proteasome system (UPS). Intriguingly, we observed similar proteolytic defects for disease-causing IVD and COX1 mutations associated with mitochondrial failure in humans. Together, these results identify a conserved link between mitochondrial metabolism and ubiquitin-dependent proteostasis. Reduced UPS activity during pathological conditions might potentiate disease progression and thus provides a valuable target for therapeutic intervention.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Segref, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kevei, EvaUNSPECIFIEDorcid.org/0000-0002-0560-9208UNSPECIFIED
Pokrzywa, WojciechUNSPECIFIEDorcid.org/0000-0002-5110-4462UNSPECIFIED
Schmeisser, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mansfeld, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Livnat-Levanon, NuritUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ensenauer, ReginaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glickman, Michael H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ristow, MichaelUNSPECIFIEDorcid.org/0000-0003-2109-2453UNSPECIFIED
Hoppe, ThorstenUNSPECIFIEDorcid.org/0000-0002-4734-9352UNSPECIFIED
URN: urn:nbn:de:hbz:38-441649
DOI: 10.1016/j.cmet.2014.01.016
Journal or Publication Title: Cell Metab.
Volume: 19
Number: 4
Page Range: S. 642 - 653
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
UBIQUITIN-PROTEASOME SYSTEM; UNFOLDED PROTEIN RESPONSE; OXIDATIVE-STRESS-RESPONSE; CYTOCHROME-C-OXIDASE; CAENORHABDITIS-ELEGANS; LIFE-SPAN; DEPENDENT PROTEOLYSIS; ISOVALERIC ACIDEMIA; OUTER-MEMBRANE; DEGRADATIONMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/44164

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item