RETRACTED: Activation of the PPAR/PGC-1α pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype (Retracted article. See vol. 24, pg. 889, 2016)

被引:245
作者
Wenz, Tina [1 ]
Diaz, Francisca [1 ]
Spiegelman, Bruce M. [3 ,4 ]
Moraes, Carlos T. [1 ,2 ]
机构
[1] Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA
[2] Univ Miami, Sch Med, Dept Cell Biol & Anat, Miami, FL 33136 USA
[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
[4] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
关键词
D O I
10.1016/j.cmet.2008.07.006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 gamma (PPAR gamma) coactivator alpha (PGC-1 alpha) in skeletal muscle or by administration of bezafibrate, a PPAR panagonist. 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 life span. Thus, induction of mitochondrial biogenesis through pharmacological or metabolic modulation of the PPAR/PGC-1 alpha pathway promises to be an effective therapeutic approach for mitochondrial disorders.
引用
收藏
页码:249 / 256
页数:8
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