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Mitochondrial myopathy induces a starvation-like response
Research Program of Molecular Neurology, Biomedicum-Helsinki, Helsinki, Finland.
Research Program of Molecular Neurology, Biomedicum-Helsinki, Helsinki, Finland.
Research Program of Molecular Neurology, Biomedicum-Helsinki, Helsinki, Finland.
Research Program of Molecular Neurology, Biomedicum-Helsinki, Helsinki, Finland.
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2010 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 19, no 20, p. 3948-3958Article in journal (Refereed) Published
Abstract [en]

Mitochondrial respiratory chain (RC) deficiency is among the most common causes of inherited metabolic disease, but its physiological consequences are poorly characterized. We studied the skeletal muscle gene expression profiles of mice with late-onset mitochondrial myopathy. These animals express a dominant patient mutation in the mitochondrial replicative helicase Twinkle, leading to accumulation of multiple mtDNA deletions and progressive subtle RC deficiency in the skeletal muscle. The global gene expression pattern of the mouse skeletal muscle showed induction of pathways involved in amino acid starvation response and activation of Akt signaling. Furthermore, the muscle showed induction of a fasting-related hormone, fibroblast growth factor 21 (Fgf21). This secreted regulator of lipid metabolism was also elevated in the mouse serum, and the animals showed widespread changes in their lipid metabolism: small adipocyte size, low fat content in the liver and resistance to high-fat diet. We propose that RC deficiency induces a mitochondrial stress response, with local and global changes mimicking starvation, in a normal nutritional state. These results may have important implications for understanding the metabolic consequences of mitochondrial myopathies.

Place, publisher, year, edition, pages
Oxford University Press, 2010. Vol. 19, no 20, p. 3948-3958
Keywords [en]
Mitochondrial myopathies, signal transduction, mutation, mitochondria, amino acids, stress response, diet, hormones, adipocytes, dna, mitochondrial, fasting, gene expression profiling, skeletal muscles, liver, mice, proto-oncogene proteins c-akt
National Category
Other Basic Medicine
Identifiers
URN: urn:nbn:se:oru:diva-70961DOI: 10.1093/hmg/ddq310ISI: 000282439700005PubMedID: 20656789Scopus ID: 2-s2.0-77957743736OAI: oai:DiVA.org:oru-70961DiVA, id: diva2:1345854
Available from: 2019-08-26 Created: 2019-08-26 Last updated: 2019-08-28Bibliographically approved

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Oresic, Matej

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