Pyruvate induces mitochondrial biogenesis by a PGC-1 alpha-independent mechanism.
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 to achieve the 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 h. Treated cells exhibited increased mitochondrial protein expression, basal respiratory rate, and maximal oxidative capacity. The increase in mitochondrial biogenesis was independent of increases in peroxisomal proliferator activator receptor-gamma coactivator-1alpha (PGC-1alpha) and PGC-1beta mRNA expression. To further assess whether PGC-1alpha expression was necessary for pyruvate action, cells were infected with adenovirus containing shRNA for PGC-1alpha before treatment with pyruvate. Despite a 70% reduction in PGC-1alpha mRNA, the effect of pyruvate was preserved. Furthermore, pyruvate induced mitochondrial biogenesis in primary myoblasts from PGC-1alpha null mice. These data suggest that regulation of mitochondrial biogenesis by pyruvate in myoblasts is independent of PGC-1alpha, suggesting the existence of a novel energy-sensing pathway regulating oxidative capacity.
Wilson
Leanne
L
Novartis Institutes for BioMedical Research, 100 Technology Square, Cambridge, MA 02139, USA.
Yang
Qing
Q
Szustakowski
Joseph D
JD
Gullicksen
P Scott
PS
Halse
Reza
R
D000222:Adaptation, Physiological; D000818:Animals; D019069:Cell Respiration; D004734:Energy Metabolism / Q000187:drug effects; D015870:Gene Expression; D020869:Gene Expression Profiling; D051379:Mice; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D053142:Mitochondrial Size; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014176:Protein Biosynthesis / Q000187:drug effects; D019289:Pyruvic Acid / Q000378:metabolism* / Q000494:pharmacology; D034622:RNA Interference; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D019289:Pyruvic Acid