This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.We initiated efforts to characterize the sequence of events in mitochondria during apoptosis to better understand models of heart disease. The relationship between mitochondria and disease is becoming increasingly important, and numerous questions remain regarding mitochondrial structure and function and possible treatments that our work attempts to answer. The important points we are clarifying are (1) Whether the permeability transition occurs before or after cytochrome c release and (2) Whether the inner membrane 'remodels' following the permeability transition to facilitate cytochrome c release as suggested by Korsmeyer's group (collaborating with Carmen Mannella). We are using cells transfected with fluorescent cytochrome c fusion proteins produced by Doug Green's lab. Another key issue we are exploring is the timing of mitochondrial swelling. A current hypothesis is that damage to mitochondria due to reactive oxygen species (ROS) is often generated by defective electron transport. The role of the permeability transition, cytochrome c release, and apoptosis in ROS damage are currently being investigated. In collaboration with Dr. Perkins, we are conducting a structural analysis of perturbed mitochondria by EM tomography. This study is envisioned to significantly aid in understanding the extent of structural alterations occurring during ROS damage, cytochrome c release, and apoptosis.Another project is based on our new collaboration with Dr. Perkins coming out of the recent meeting on Mitochondrial Diseases in San Diego. . Our current hypothesis is that damage to mitochondria due to reactive oxygen species (ROS) is often generated by defective electron transport. The role of the permeability transition, cytochrome c release, and apoptosis in ROS damage is being investigated. In relation to muscular dystrophy, Immo Scheffler?s cell culture model systems for mitochondrial diseases are being applied. In addition, the work of Lee-Jun Wong from Georgetown University who has biopsy samples from mitochondrial disease patients is aiding these studies. We have yet to acquire a structural analysis of mitochondria by EM tomography. However, this 3-D technique is envisioned to significantly aid an understanding as to the extent of structural alterations occurring during ROS damage and apoptosis.
Showing the most recent 10 out of 270 publications
