Mitochondrial misreading in skeletal muscle accelerates metabolic aging and confers lipid accumulation and increased inflammation
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Date
2021-03
Publication Type
Journal Article
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Abstract
We have recently reported on an experimental model of mitochondrial mistranslation conferred by amino acid exchange V338Y in 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 postmitotic skeletal muscle. Metabolome analysis demonstrated enhanced levels of age-associated metabolites in the mutant V338Y animals 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 impairment of mitochondrial function affects specific bioenergetic processes in muscle in an age-dependent manner.
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published
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Journal / series
Volume
27 (3)
Pages / Article No.
265 - 272
Publisher
Cold Spring Harbor Laboratory
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Subject
Mitochondria; Misreading; Skeletal muscle; Aging; Metabolome
Organisational unit
02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich