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000163786 1001_ $$0P:(DE-2719)2811171$$aPiazzesi, Antonia$$b0$$eFirst author
000163786 245__ $$aCEST‐2.2 overexpression alters lipid metabolism and extends longevity of mitochondrial mutants
000163786 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2022
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000163786 520__ $$aMitochondrial dysfunction can either extend or decrease Caenorhabditis elegans lifespan, depending on whether transcriptionally regulated responses can elicit durable stress adaptation to otherwise detrimental lesions. Here, we test the hypothesis that enhanced metabolic flexibility is sufficient to circumvent bioenergetic abnormalities associated with the phenotypic threshold effect, thereby transforming short-lived mitochondrial mutants into long-lived ones. We find that CEST-2.2, a carboxylesterase mainly localizes in the intestine, may stimulate the survival of mitochondrial deficient animals. We report that genetic manipulation of cest-2.2 expression has a minor lifespan impact on wild-type nematodes, whereas its overexpression markedly extends the lifespan of complex I-deficient gas-1(fc21) mutants. We profile the transcriptome and lipidome of cest-2.2 overexpressing animals and show that CEST-2.2 stimulates lipid metabolism and fatty acid beta-oxidation, thereby enhancing mitochondrial respiratory capacity through complex II and LET-721/ETFDH, despite the inherited genetic lesion of complex I. Together, our findings unveil a metabolic pathway that, through the tissue-specific mobilization of lipid deposits, may influence the longevity of mitochondrial mutant C. elegans.
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000163786 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x2
000163786 588__ $$aDataset connected to CrossRef, Journals: pub.dzne.de
000163786 650_2 $$2MeSH$$aAnimals
000163786 650_2 $$2MeSH$$aCaenorhabditis elegans: metabolism
000163786 650_2 $$2MeSH$$aCaenorhabditis elegans Proteins: genetics
000163786 650_2 $$2MeSH$$aCaenorhabditis elegans Proteins: metabolism
000163786 650_2 $$2MeSH$$aLipid Metabolism: genetics
000163786 650_2 $$2MeSH$$aLongevity: genetics
000163786 650_2 $$2MeSH$$aMitochondria: metabolism
000163786 7001_ $$0P:(DE-2719)9001250$$aWang, Yiru$$b1
000163786 7001_ $$0P:(DE-2719)2814190$$aJackson, Joshua$$b2
000163786 7001_ $$0P:(DE-2719)2811527$$aWischhof, Lena$$b3
000163786 7001_ $$aZeisler-Diehl, Viktoria$$b4
000163786 7001_ $$0P:(DE-2719)2812562$$aScifo, Enzo$$b5
000163786 7001_ $$0P:(DE-2719)9001607$$aOganezova, Ina$$b6
000163786 7001_ $$0P:(DE-2719)2813300$$aHoffmann, Nils Thorben$$b7
000163786 7001_ $$0P:(DE-2719)9002156$$aGomez, Pablo$$b8$$udzne
000163786 7001_ $$0P:(DE-2719)2810664$$aBertan, Fabio$$b9
000163786 7001_ $$aWrobel, Chester J J$$b10
000163786 7001_ $$aSchroeder, Frank C$$b11
000163786 7001_ $$0P:(DE-2719)2289209$$aEhninger, Dan$$b12
000163786 7001_ $$0P:(DE-2719)2812735$$aHändler, Kristian$$b13
000163786 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b14
000163786 7001_ $$00000-0001-7003-9929$$aSchreiber, Lukas$$b15
000163786 7001_ $$00000-0002-2816-7852$$aEchten-Deckert, Gerhild$$b16
000163786 7001_ $$0P:(DE-2719)2010732$$aNicotera, Pierluigi$$b17
000163786 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b18$$eLast author
000163786 773__ $$0PERI:(DE-600)2025376-X$$a10.15252/embr.202152606$$n5$$pe52606$$tEMBO reports$$v23$$x1469-221X$$y2022
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