Mitochondrial misreading in skeletal muscle accelerates metabolic aging and confers lipid accumulation and increased inflammation.
Aging
Metabolome
Misreading
Mitochondria
Skeletal Muscle
Journal
RNA (New York, N.Y.)
ISSN: 1469-9001
Titre abrégé: RNA
Pays: United States
ID NLM: 9509184
Informations de publication
Date de publication:
01 Dec 2020
01 Dec 2020
Historique:
received:
20
07
2020
accepted:
23
11
2020
entrez:
2
12
2020
pubmed:
3
12
2020
medline:
3
12
2020
Statut:
aheadofprint
Résumé
We have recently reported on an experimental model of mitochondrial mistranslation conferred by amino acid exchange V338Y in the mitochondrial ribosomal protein MrpS5. Here we used a combination of RNA-Seq and metabolic profiling of homozygous transgenic MrpS5V338Y/V338Y mice to analyze the changes associated with the V338Y mutation in post-mitotic skeletal muscle. Metabolic profiling demonstrated age-dependent metabolic changes in the mutant V338Y animals, which included enhanced levels of age-associated metabolites and which were accompanied by increased glycolysis, lipid desaturation and eicosanoid biosynthesis, and alterations of the pentose phosphate pathway. In addition, transcriptome signatures of aged V338Y mutant muscle pointed to elevated inflammation, likely reflecting the increased levels of bioactive lipids. Our findings indicate that mistranslation-mediated chronic impairment of mitochondrial function affects specific bioenergetic processes in muscle in an age-dependent manner.
Identifiants
pubmed: 33262249
pii: rna.077347.120
doi: 10.1261/rna.077347.120
pmc: PMC7901843
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Published by Cold Spring Harbor Laboratory Press for the RNA Society.
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