Submitted on August 10, 2006
Accepted on December 19, 2006
Pyruvate induces mitochondrial biogenesis by a PGC-1
independent mechanism
Leanne Wilson1, Qing Yang1, Scott P Gullicksen2, and Reza Halse1*
1 Diabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, United States
2 Department of Diabetes & Metabolism, Novartis Institutes for Biomedical Resources, Cambridge, Massachusetts, 02139, United States
* To whom correspondence should be addressed. E-mail: reza.halse{at}novartis.com.
Oxidative cells increase mitochondrial mass in response to stimuli such as changes in energy demand or cellular differentiation. This plasticity enables the cell to adapt dynamically in order to achieve necessary oxidative capacity. However, the pathways involved in triggering mitochondrial biogenesis are poorly defined. The present study examines the impact of altering energy provision on mitochondrial biogenesis in muscle cells. C2C12 myoblasts were chronically treated with supraphysiological levels of sodium pyruvate for 72 hr. Treated cells exhibited increased mitochondrial protein expression, basal respiratory rate and maximal oxidative capacity. The increase in mitochondrial biogenesis was independent of increases in PGC-1
and PGC-1
mRNA expression. To further assess whether PGC-1 expression was necessary for pyruvate action, cells were infected with adenovirus containing shRNA for PGC-1prior to treatment with pyruvate. Despite a 70% reduction in PGC-1 mRNA the effect of pyruvate was preserved. Furthermore, pyruvate induced mitochondrial biogenesis in primary myoblasts from PGC-1 null mice. These data suggest that regulation of mitochondrial biogenesis by pyruvate in myoblasts is independent of PGC-1, suggesting the existence of a novel energy-sensing pathway regulating oxidative capacity.
