92899
The Effects of Estrogen on Mitochondrial Biogenesis
Dumindra Gurusinghe
Mentor: Vincent Procaccio
The decline of mitochondrial biogenesis characterizes many metabolic and age-related diseases such as stroke. As a result, the PGC-1 family of transcriptional co-activators, widely implicated in the regulation of energy metabolism, and isoform PCG-1α in particular, has been subject to much study. PGC-1α co-regulates oxidative phosphorylation, the mitochondrially-set energy-generating process of aerobic organisms. Our lab has shown that estrogen-related therapies, which induce mitochondrial biogenesis, down-regulate PGC-1α and up-regulate its isoform PGC1-β (PERC) in cerebral blood vessels. Moreover, their positive effects on biogenesis do not rely on PCG-1α. Estrogen-related compounds then potentially bear therapeutic benefits for patients with mitochondrial disorders. Currently, the role of PERC in the estrogen pathway has not been fully described. To address this, I treated cerebral endothelial and fibroblast cells with estrogen and monitored the change in gene and protein expression of mitochondrial proteins known to be induced: cytochrome c, complex IV, and manganese superoxide dismutase. I then compared the relative change in biogenesis between cell lines bearing mitochondrial DNA mutations versus controls. Preliminary data suggests that estrogen treatment up-regulates cytochrome c, manganese superoxide, and complex IV expression at both the gene and the protein level, providing insight into how estrogen and estrogen-related therapies impact mitochondrial function.