PGC-1alpha/beta induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders.

Abstract	Members of the peroxisome proliferator-activated receptor gamma coactivator (PGC) family are potent inducers of mitochondrial biogenesis. We have tested the potential effect of increased mitochondrial biogenesis in cells derived from patients harboring oxidative phosphorylation defects due to either nuclear or mitochondrial DNA mutations. We found that the PGC-1alpha and/or PGC-1beta expression improved mitochondrial respiration in cells harboring a complex III or IV deficiency as well as in transmitochondrial cybrids harboring mitochondrial encephalomyopathy lactic acidosis and stroke A3243G tRNA((Leu)UUR) gene mutation. The respiratory function improvement was found to be associated with increased levels of mitochondrial components per cell, although this increase was not homogeneous. These results reinforce the concept that increased mitochondrial biogenesis is a promising venue for the treatment of mitochondrial diseases.
Authors	Sarika Srivastava, Francisca Diaz, Luisa Iommarini, Karine Aure, Anne Lombes, Carlos T Moraes
Journal	Human molecular genetics (Hum Mol Genet) Vol. 18 Issue 10 Pg. 1805-12 (May 15 2009) ISSN: 1460-2083 [Electronic] England
PMID	19297390 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins Heat-Shock Proteins PPARGC1A protein, human PPARGC1B protein, human Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha RNA-Binding Proteins Transcription Factors
Topics	Carrier Proteins (genetics, metabolism) Cell Respiration Cells, Cultured Child, Preschool Electron Transport Female Fibroblasts (metabolism) Gene Expression Heat-Shock Proteins (genetics, metabolism) Humans Infant Male Mitochondria (genetics, metabolism) Mitochondrial Diseases (genetics, metabolism) Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha RNA-Binding Proteins Transcription Factors (genetics, metabolism) Up-Regulation

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