Description:

The Department of Biochemistry & Molecular Genetics presents:

Kathryn E Wellen, PhD
Professor of Cancer Biology
Vice Chair, Department of Cancer Biology
Abramson Family Cancer Research Institute
Penn Epigenetics Institute 
University of Pennsylvania Perelman School of Medicine

Presentation:

"The roles of acetyl-CoA in metabolic signaling and tissue homeostasis"

Abstract:

Acetyl-CoA is a central metabolic intermediate generated during nutrient catabolism and used for lipid synthesis in the cytosol and histone acetylation in the nucleus.  Acetyl-CoA-producing metabolic enzymes, including ATP-citrate lyase (ACLY) and the cytosolic acetyl-CoA synthetase (ACSS2), have garnered substantial interest as therapeutic targets for metabolic diseases and cancer.  However, key questions relevant to targeting these enzymes remain incompletely understood, including the roles and regulation of metabolic compensatory pathways for acetyl-CoA production, as well as the essential, non-redundant functions of each enzyme in physiology.   In this presentation, I will discuss our efforts to understand metabolic flexibility mechanisms for acetyl-CoA production in the regulation of lipid synthesis and histone acetylation.  I will also discuss new data that reveal a role for ACLY in skin homeostasis and suggest that acetyl-CoA synthesis in the skin may be an important determinant of systemic lipid partitioning.  Together, the data highlight the remarkable capacity of cells and organisms to engage metabolic compensatory mechanisms to sustain crucial functions, but also point to costs and trade-offs, potentially helping to inform the use of lipid metabolism inhibitors.

Host: Dr. Lillian J Eichner, Assistant Professor of Biochemistry and Molecular Genetics