Home > Publications Database > CEST‐2.2 overexpression alters lipid metabolism and extends longevity of mitochondrial mutants > print

001     163786
005     20240320115522.0
024 7 _ |a pmc:PMC9066074
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024 7 _ |a 1469-221X
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100 1 _ |a Piazzesi, Antonia
|0 P:(DE-2719)2811171
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245 _ _ |a CEST‐2.2 overexpression alters lipid metabolism and extends longevity of mitochondrial mutants
260 _ _ |a Hoboken, NJ [u.a.]
|c 2022
|b Wiley
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520 _ _ |a Mitochondrial 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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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Caenorhabditis elegans: metabolism
|2 MeSH
650 _ 2 |a Caenorhabditis elegans Proteins: genetics
|2 MeSH
650 _ 2 |a Caenorhabditis elegans Proteins: metabolism
|2 MeSH
650 _ 2 |a Lipid Metabolism: genetics
|2 MeSH
650 _ 2 |a Longevity: genetics
|2 MeSH
650 _ 2 |a Mitochondria: metabolism
|2 MeSH
700 1 _ |a Wang, Yiru
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700 1 _ |a Jackson, Joshua
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700 1 _ |a Wischhof, Lena
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700 1 _ |a Zeisler-Diehl, Viktoria
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700 1 _ |a Scifo, Enzo
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700 1 _ |a Oganezova, Ina
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700 1 _ |a Hoffmann, Nils Thorben
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700 1 _ |a Gomez, Pablo
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700 1 _ |a Bertan, Fabio
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700 1 _ |a Wrobel, Chester J J
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700 1 _ |a Schroeder, Frank C
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700 1 _ |a Ehninger, Dan
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700 1 _ |a Händler, Kristian
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700 1 _ |a Schultze, Joachim L
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700 1 _ |a Schreiber, Lukas
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700 1 _ |a Echten-Deckert, Gerhild
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700 1 _ |a Nicotera, Pierluigi
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700 1 _ |a Bano, Daniele
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