Biogenesis of functional and competent mitochondria requires the import and assembly of more than 1,000 proteins synthesized mostly in the cytoplasm and few in the mitochondria. The dynamics of mitochondrial formation and assembly is a complex cellular process that ultimately shapes the bioenergetic capacity. Mitochondrial biogenesis is heavily dependent upon timely and coordinated control of genes encoding for mitochondrial proteins.
Our laboratory is interested in the major signals and dominant regulatory components that program mitochondrial biogenesis, integrity, and bioenergetic activities. This regulatory network provides a therapeutic window to treat a broad spectrum of diseases associated with mitochondrial dysregulation, including metabolic diseases, myopathies and neurodegenerative diseases. The central questions include the identification of the components that sense extra- and intracellular signals to coordinate the supply of proteins that assemble mitochondrial processes.
We use traditional approaches in biochemistry, cellular biology and physiology in combination with new screening technologies, genetic/epigenetic and disease models. We have applied bioinformatic and genetic/proteomic tools to identify transcription factors that are pivotal to mitochondrial biology including the zinc finger YY1 and the co-activator PGC-1α.
Mol Cell. 64(1):163-175, 2016
Mitochondrial biogenesis through activation of nuclear signaling proteins
J. E. Dominy and P. Puigserver
Cold Spring Harb Perspect Biol. 5(7), 2013
Defective mitochondrial dynamics and bioenergetic function in mice lacking the transcription factor YY1 in skeletal muscle
S.M. Blättler, F. Verdeguer, J.T. Cunningham, H. Chim, M. Ruegg, Y. Shi and P. Puigserver
Mol Cell Biol. 32(16):3333-46,2012
mTOR controls mitochondrial oxidative function through a YY1/PGC-1α complex.
J.T. Cunningham, J.T. Rodgers, D. Arlow, F. Vazquez, V.K. Mootha and P. Puigserver
Nature. 450, 736-740, 2007
Metabolic control of mitochondrial function and fatty acid oxidation through PGC-1α/SIRT1
Z. Gerhart-Hines, J.T. Rodgers, O. Bare, C. Lerin, S.H. Kim, R. Mostoslavsky, F.W. Alt, Z. Wu and P. Puigserver
EMBO J. 26, 1913-1923, 2007