Abstract
Mitochondria are one of the most complex of subcellular organelles and play key roles in many cellular functions including energy production, fatty acid metabolism, pyrimidine biosynthesis, calcium homeostasis and cell signaling. In recent years, there has been a significant increase in studies pointing to an important, if not central, role for mitochondria in normal aging as well as age-related diseases such as cancer and Parkinson's disease. In an effort to provide a more detailed molecular understanding of mitochondria in aging and disease, and to better understand its cellular functions, we and other groups have initiated mass spectrometry-based proteomic studies to identify the complete set of proteins that are localized to human mitochondria. In this presentation, I will describe some of our efforts at determining the human mitochondrial proteome with an emphasis towards understanding how mitochondrial proteins, especially the proteins that make up the respiratory chain (Complex I-V), are modified in various models of aging and age-related diseases. Particular focus will be given to understanding the molecular details of oxidative stress and the mitochondrial role in this process, as well as the development of new proteomic tools to assess how mitochondrial proteins become oxidatively damaged and/or post-translationally modified.
 
Background
Dr. Gibson received his doctorate from MIT under the supervision of Dr. Klaus Biemann on applications of mass spectrometry to protein structure determination. As a postdoctoral fellow at Cambridge University he continued to advance the application of mass spectrometry to protein analysis that included studies on the regulation of phosphorylation sites in glycogen synthetase (with Philip Cohen, Univ. Dundee), the analysis of posttranslational modifications in mitochondrial proteins (with John Walker, MRC Cambridge) and the identification of a novel class of bioactive peptides hormones in the laboratory of Dr. Dudley Williams. In 1985, Dr. Gibson became a faculty member in the Department of Pharmaceutical Chemistry at UCSF where, over a 15-year period, he applied mass spectrometry to problems ranging from bacterial pathogenesis to the tertiary structure of proteins. In collaboration with his colleagues at UCSF, for example, he pioneered the use of chemical crosslinking strategies for determining tertiary structures of proteins. In 2000, Dr. Gibson joined the Buck Institute of Age Research in Novato, CA as Professor and Director of Chemistry and started a new program in mass spectrometry-based proteomics. At the Buck Institute, Dr. Gibson has shifted his focus to study the basic biology of aging and age-related diseases. These applications encompass a broad array of topics centered on neurodegenerative disease (e.g., Huntington's and Parkinson's disease), cancer and basic mechanisms of aging. One central focus has been on studying role of mitochondria in these processes, and Dr. Gibson and his colleagues have published extensively on the mitochondrial proteome, the electron transport chain complexes, oxidative stress and protein phosphorylation.