Activation of the PPAR/PGC-1alpha pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype.
Activation of the PPAR/PGC-1alpha pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype.
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DOI：
10.1016/j.cmet.2008.07.006
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发表时间：
2008-09
期刊：
影响因子：
29
通讯作者：
Moraes CT
中科院分区：
文献类型：
--
作者：
Wenz T;Diaz F;Spiegelman BM;Moraes CT
Neuromuscular disorders with defects in the mitochondrial ATP generating system affect a large number of children and adults worldwide, but remain without treatment. We used a mouse model of mitochondrial myopathy, caused by a cytochrome c oxidase deficiency, to evaluate the effect of induced mitochondrial biogenesis on the course of the disease. Mitochondrial biogenesis was induced either by transgenic expression of peroxisome proliferator activated receptor γ (PPARγ) coactivator α (PGC-1α) in skeletal muscle or by administration of bezafibrate, a PPAR pan-agonist. Both strategies successfully stimulated residual respiratory capacity in muscle tissue. Mitochondrial proliferation resulted in an enhanced OXPHOS capacity per muscle mass. As a consequence, ATP levels were conserved resulting in a delayed onset of the myopathy and a markedly prolonged live span. Thus, induction of mitochondrial biogenesis through pharmacological or metabolic modulation of the PPAR/PGC-1α pathway promises to be an effective therapeutic approach for mitochondrial disorders.
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影响因子：
4
作者：
DiMauro, Salvatore;Mancuso, Michelangelo
通讯作者：
Mancuso, Michelangelo
影响因子：
3.3
作者：
Calvo, Jennifer A.;Daniels, Thomas G.;Rangwala, Shamina M.
通讯作者：
Rangwala, Shamina M.
影响因子：
10.5
作者：
Handschin, Christoph;Kobayashi, Yvonne M.;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
4.8
作者：
Handschin, Christoph;Chin, Sherry;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
DOI：
10.1073/pnas.0401401101
发表时间：
2004-04-27
影响因子：
11.1
作者：
Mootha, VK;Handschin, C;Spiegelman, BM
通讯作者：
Spiegelman, BM