Becker 2018 EMBO Rep

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Becker C, Kukat A, Szczepanowska K, Hermans S, Senft K, Brandscheid CP, Maiti P, Trifunovic A (2018) CLPP deficiency protects against metabolic syndrome but hinders adaptive thermogenesis. EMBO Rep 19. pii: e45126.

» PMID: 29588285

Becker C, Kukat A, Szczepanowska K, Hermans S, Senft K, Brandscheid CP, Maiti P, Trifunovic A (2018) EMBO Rep

Abstract: Mitochondria are fundamental for cellular metabolism as they are both a source and a target of nutrient intermediates originating from converging metabolic pathways, and their role in the regulation of systemic metabolism is increasingly recognized. Thus, maintenance of mitochondrial homeostasis is indispensable for a functional energy metabolism of the whole organism. Here, we report that loss of the mitochondrial matrix protease CLPP results in a lean phenotype with improved glucose homeostasis. Whole-body CLPP-deficient mice are protected from diet-induced obesity and insulin resistance, which was not present in mouse models with either liver- or muscle-specific depletion of CLPP. However, CLPP ablation also leads to a decline in brown adipocytes function leaving mice unable to cope with a cold-induced stress due to non-functional adaptive thermogenesis. These results demonstrate a critical role for CLPP in different metabolic stress conditions such as high-fat diet feeding and cold exposure providing tools to understand pathologies with deregulated Clpp expression and novel insights into therapeutic approaches against metabolic dysfunctions linked to mitochondrial diseases.

Keywords: VLCAD, CLPP deficiency, Fatty acid oxidation, Metabolism, Thermogenesis Bioblast editor: Kandolf G O2k-Network Lab: DE Cologne Trifunovic A

Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine 

Stress:Temperature, Mitochondrial disease  Organism: Mouse  Tissue;cell: Liver, Fat  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

Labels, 2018-05