Mitochondrial myopathy induces a starvation-like response.
Henna Tyynismaa1, Christopher J Carroll, Nuno Raimundo
1Research Program of Molecular Neurology, Biomedicum-Helsinki, 00290 Helsinki, Finland.
Human Molecular Genetics
|July 27, 2010
Summary
Mitochondrial respiratory chain deficiency triggers a starvation-like response in skeletal muscle, impacting amino acid and lipid metabolism. This study reveals systemic metabolic changes mimicking fasting, even in well-fed mice.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Diseases
Background:
- Mitochondrial respiratory chain (RC) deficiency is a common inherited metabolic disease.
- Its physiological consequences, particularly in skeletal muscle, are not well understood.
Purpose of the Study:
- To investigate the physiological and metabolic consequences of late-onset mitochondrial myopathy.
- To characterize skeletal muscle gene expression changes in response to mitochondrial dysfunction.
Main Methods:
- Studied gene expression profiles in skeletal muscle of mice with a Twinkle mutation causing mtDNA deletions.
- Analyzed serum and tissue for metabolic changes, including lipid profiles and hormone levels.
Main Results:
- Skeletal muscle showed induction of amino acid starvation response and Akt signaling pathways.
- Fibroblast growth factor 21 (Fgf21), a fasting hormone, was elevated, alongside altered lipid metabolism (small adipocytes, low liver fat, diet resistance).
Conclusions:
- Mitochondrial RC deficiency induces a systemic mitochondrial stress response mimicking starvation.
- These findings offer insights into the metabolic dysregulation in mitochondrial myopathies.
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