Izabella A. Pena, Ph.D.

An abundance of evidence points to defects in the function of two very important components of brain cells in Huntington’s disease (HD): lysosomes and mitochondria. The lysosome is a cellular organelle known for its role as a specialized “recycling bin,” degrading damaged organelles and toxic protein aggregates. Mitochondria are widely known as the “powerhouses of the cell” due to the production of ATP, but in fact these cell components play wider roles in the production of many important molecules (e.g., building blocks to synthesize nucleotides that build our DNA and RNA). Here, I propose to determine the exact composition of lysosomes and mitochondria isolated from specific cell types in the brains of mice with HD. We have developed techniques for fast lysosome and mitochondria isolation, and I have expertise in biochemical profiling. Using these innovative technologies, we may discover novel biomolecules implicated in HD that may help us understand what is wrong in the affected neurons and may also serve as biomarkers. We aim to produce a comprehensive catalog of biomolecules that change in neurons and their compartments (lysosomes and mitochondria) in the brains of mice with HD.