Human Molecular Genetics Advance Access originally published online on March 18, 2009
Human Molecular Genetics 2009 18(10):1805-1812; doi:10.1093/hmg/ddp093
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PGC-1
/β induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders
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1 Department of Neurology 2 Department of Cell Biology and Anatomy, University of Miami School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA 3 Dipartimento di Scienze Neurologiche, Università di Bologna, Bologna, Italy 4 Inserm 582; UPMC-Paris6; AP/HP, Paris F-75013, France
* To whom correspondence should be addressed. Tel: +1 3052435858; Fax: +1 3052433914; Email: cmoraes{at}med.miami.edu
Received August 20, 2008; Revised February 3, 2009; Accepted February 24, 2009
Members of the peroxisome proliferator-activated receptor 
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-1
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.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
Present address: Harvard Medical School, Boston, MA 02115, USA.