Professor, Cell and Molecular Biology; Feinberg School of Medicine
Cancer Cell Biology
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Because of the limited coding capacity of mtDNA the nuclear genome must provide the majority of the constituents needed for mitochondrial functions, including the maintenance and expression of mtDNA. This arrangement necessitates the interplay of nuclear and mitochondrial genetic systems in meeting cellular energy demands. Previous studies have led to the discovery, purification and molecular cloning of nuclear respiratory factors (NRFs) 1 and 2. These transcriptional activators act on the majority of nuclear genes that are required for mitochondrial respiratory function. A second class of nuclear regulator is the PGC-1 family of coactivators that includes PGC-1_, PRC and PGC1_. These molecules do not bind DNA but rather work through their interactions with multiple transcription factors to regulate gene expression. Dr. Scarpulla has found an important feature of these coactivators is that their expression is responsive to physiological signals mediating adaptive thermogenesis, cell proliferation and gluconeogenesis. His recent focus has been on PRC, a NRF-1 coactivator that is rapidly up-regulated in proliferating cells and down-regulated upon exit from the cell cycle. PRC is a unique example of a growth-regulated coactivator, which acts predominantly in the G0 to G1 transition from quiescence to proliferative growth. Further characterization of PRC should provide insight into the genetic program regulating cell proliferation.