Mitochondrial myopathy induces a starvation-like response

Human Molecular Genetics
Henna TyynismaaAnu Suomalainen

Abstract

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...Continue Reading

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Citations

Jan 18, 2012·Analytical and Bioanalytical Chemistry·Martin F AlmstetterKatja Dettmer
Oct 14, 2010·Journal of Inherited Metabolic Disease·Anu Suomalainen
Feb 23, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Orest Hurko
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Apr 30, 2015·International Journal of Molecular Sciences·Michael Fasullo, Lauren Endres
Jun 21, 2013·Expert Opinion on Medical Diagnostics·Anu Suomalainen
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