Sustained AMPK activation improves muscle function in a mitochondrial myopathy mouse model by promoting muscle fiber regeneration

Susana Peralta, Sofia Garcia, Han Yang Yin, Tania Arguello, Francisca Diaz, Carlos T Moraes

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Acute pharmacological activation of adenosinemonophosphate (AMP)-kinase using 5-aminoimidazole-4-carboxamide-1-b-Dribofuranoside (AICAR) has been shown to improvemusclemitochondrial function by increasingmitochondrial biogenesis.We asked whether prolonged AICAR treatment is beneficial in amousemodel of slowly progressingmitochondrialmyopathy (Cox10-Mef2c-Cre), and whether the compensatorymechanismis indeed an increase inmitochondrial biogenesis.We treated the animals for 3months and found that sustained AMP-dependent kinase activation improved cytochrome c oxidase activity, rescued themotor phenotype and delayed the onset of themyopathy. This improvement was observed whether treatment started before or after the onset of the disease.We found that AICAR increased skeletalmuscle regeneration thereby decreasing the levels of deleted Cox10-floxed alleles.We conclude that although increase inmitochondrial biogenesis and other pathwaysmay contribute, themainmechanismby which AICAR improves themyopathy phenotype is by promotingmuscle regeneration.

Original languageEnglish (US)
Pages (from-to)3178-3191
Number of pages14
JournalHuman Molecular Genetics
Volume25
Issue number15
DOIs
StatePublished - 2015

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Mitochondrial Myopathies
AMP-Activated Protein Kinases
Regeneration
Muscles
Phosphotransferases
Aminoimidazole Carboxamide
Phenotype
Electron Transport Complex IV
Alleles
Pharmacology
AICA ribonucleotide

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Sustained AMPK activation improves muscle function in a mitochondrial myopathy mouse model by promoting muscle fiber regeneration. / Peralta, Susana; Garcia, Sofia; Yin, Han Yang; Arguello, Tania; Diaz, Francisca; Moraes, Carlos T.

In: Human Molecular Genetics, Vol. 25, No. 15, 2015, p. 3178-3191.

Research output: Contribution to journalArticle

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AU - Diaz, Francisca

AU - Moraes, Carlos T

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