PGC-1α/β induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders

Sarika Srivastava, Francisca Diaz, Luisa Iommarini, Karine Aure, Anne Lombes, Carlos T Moraes

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Members of the peroxisome proliferator-activated receptor γ 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-1α and/or PGC-1β 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.

Original languageEnglish
Pages (from-to)1805-1812
Number of pages8
JournalHuman Molecular Genetics
Volume18
Issue number10
DOIs
StatePublished - May 7 2009

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Mitochondrial Diseases
Organelle Biogenesis
Electron Transport
Mitochondrial Encephalomyopathies
RNA, Transfer, Leu
Cell Respiration
Lactic Acidosis
Mutation
Peroxisome Proliferator-Activated Receptors
Electron Transport Complex III
Oxidative Phosphorylation
Cellular Structures
Mitochondrial DNA
Stroke
Genes
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

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PGC-1α/β induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders. / Srivastava, Sarika; Diaz, Francisca; Iommarini, Luisa; Aure, Karine; Lombes, Anne; Moraes, Carlos T.

In: Human Molecular Genetics, Vol. 18, No. 10, 07.05.2009, p. 1805-1812.

Research output: Contribution to journalArticle

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