Universität zu Köln

Kukat, Alexandra, Dogan, Sukru Anil ORCID: 0000-0002-1800-2923, Edgar, Daniel, Mourier, Arnaud, Jacoby, Christoph, Maiti, Priyanka ORCID: 0000-0003-4207-0341, Mauer, Jan ORCID: 0000-0002-0189-5876, Becker, Christina, Senft, Katharina, Wibom, Rolf, Kudin, Alexei P., Hultenby, Kjell, Floegel, Ulrich, Rosenkranz, Stephan, Ricquier, Daniel, Kunz, Wolfram S. ORCID: 0000-0003-1113-3493 and Trifunovic, Aleksandra (2014). Loss of UCP2 Attenuates Mitochondrial Dysfunction without Altering ROS Production and Uncoupling Activity. PLoS Genet., 10 (6). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7404

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Abstract

Although mitochondrial dysfunction is often accompanied by excessive reactive oxygen species (ROS) production, we previously showed that an increase in random somatic mtDNA mutations does not result in increased oxidative stress. Normal levels of ROS and oxidative stress could also be a result of an active compensatory mechanism such as a mild increase in proton leak. Uncoupling protein 2 (UCP2) was proposed to play such a role in many physiological situations. However, we show that upregulation of UCP2 in mtDNA mutator mice is not associated with altered proton leak kinetics or ROS production, challenging the current view on the role of UCP2 in energy metabolism. Instead, our results argue that high UCP2 levels allow better utilization of fatty acid oxidation resulting in a beneficial effect on mitochondrial function in heart, postponing systemic lactic acidosis and resulting in longer lifespan in these mice. This study proposes a novel mechanism for an adaptive response to mitochondrial cardiomyopathy that links changes in metabolism to amelioration of respiratory chain deficiency and longer lifespan.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kukat, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Dogan, Sukru Anil UNSPECIFIED orcid.org/0000-0002-1800-2923 UNSPECIFIED Edgar, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Mourier, Arnaud UNSPECIFIED UNSPECIFIED UNSPECIFIED Jacoby, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Maiti, Priyanka UNSPECIFIED orcid.org/0000-0003-4207-0341 UNSPECIFIED Mauer, Jan UNSPECIFIED orcid.org/0000-0002-0189-5876 UNSPECIFIED Becker, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Senft, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wibom, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kudin, Alexei P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hultenby, Kjell UNSPECIFIED UNSPECIFIED UNSPECIFIED Floegel, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenkranz, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ricquier, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Kunz, Wolfram S. UNSPECIFIED orcid.org/0000-0003-1113-3493 UNSPECIFIED Trifunovic, Aleksandra UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-436417
DOI:	10.1371/journal.pgen.1004385
Journal or Publication Title:	PLoS Genet.
Volume:	10
Number:	6
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7404
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language OXIDATIVE STRESS; REGULATING GLUCOSE; PROTEIN-2 UCP2; LIFE-SPAN; MICE; DNA; HEART; OVEREXPRESSION; CARDIOMYOPATHY; LIPOTOXICITY Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43641