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of the PPAR/PGC-1α pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype (Retracted article.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)
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.
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA
Harvard Stem Cell Inst, Boston, MA 02215 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Arany, Zoltan
Foo, Shi-Yin
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Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA
Harvard Stem Cell Inst, Boston, MA 02215 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Foo, Shi-Yin
Ma, Yanhong
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Ma, Yanhong
Ruas, Jorge L.
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Ruas, Jorge L.
Bommi-Reddy, Archana
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Bommi-Reddy, Archana
Girnun, Geoffrey
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Girnun, Geoffrey
Cooper, Marcus
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Cooper, Marcus
Laznik, Dina
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Laznik, Dina
Chinsomboon, Jessica
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Chinsomboon, Jessica
Rangwala, Shamina M.
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Novartis Inst Biomed Res Diabet & Metab, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Rangwala, Shamina M.
Baek, Kwan Hyuck
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Harvard Univ, Sch Med, Vasc Biol Program, Dept Surg,Childrens Hosp, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Baek, Kwan Hyuck
Rosenzweig, Anthony
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Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA
Harvard Stem Cell Inst, Boston, MA 02215 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Rosenzweig, Anthony
Spiegelman, Bruce M.
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Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA
Harvard Stem Cell Inst, Boston, MA 02215 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Arany, Zoltan
Foo, Shi-Yin
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机构:
Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA
Harvard Stem Cell Inst, Boston, MA 02215 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Foo, Shi-Yin
Ma, Yanhong
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机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Ma, Yanhong
Ruas, Jorge L.
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机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Ruas, Jorge L.
Bommi-Reddy, Archana
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机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Bommi-Reddy, Archana
Girnun, Geoffrey
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机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Girnun, Geoffrey
Cooper, Marcus
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机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Cooper, Marcus
Laznik, Dina
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机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Laznik, Dina
Chinsomboon, Jessica
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h-index: 0
机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Chinsomboon, Jessica
Rangwala, Shamina M.
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h-index: 0
机构:
Novartis Inst Biomed Res Diabet & Metab, Cambridge, MA 02139 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Rangwala, Shamina M.
Baek, Kwan Hyuck
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Vasc Biol Program, Dept Surg,Childrens Hosp, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Baek, Kwan Hyuck
Rosenzweig, Anthony
论文数: 0引用数: 0
h-index: 0
机构:
Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA
Harvard Stem Cell Inst, Boston, MA 02215 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Rosenzweig, Anthony
Spiegelman, Bruce M.
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h-index: 0
机构:
Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USAHarvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA