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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR008605-15
Application #
7722314
Study Section
Special Emphasis Panel (ZRG1-SSS-9 (40))
Project Start
2008-05-01
Project End
2009-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
15
Fiscal Year
2008
Total Cost
$3,233
Indirect Cost
Name
University of California San Diego
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Pantoja, Joe Luis; Morgan, Ashley E; Grossi, Eugene A et al. (2017) Undersized Mitral Annuloplasty Increases Strain in the Proximal Lateral Left Ventricular Wall. Ann Thorac Surg 103:820-827
Morgan, Ashley E; Wozniak, Curtis J; Gulati, Sarthak et al. (2017) Association of Uneven MitraClip Application and Leaflet Stress in a Finite Element Model. JAMA Surg 152:111-114
Ge, Liang; Wu, Yife; Soleimani, Mehrdad et al. (2016) Moderate Ischemic Mitral Regurgitation After Posterolateral Myocardial Infarction in Sheep Alters Left Ventricular Shear but Not Normal Strain in the Infarct and Infarct Borderzone. Ann Thorac Surg 101:1691-9
Morgan, Ashley E; Pantoja, Joe Luis; Weinsaft, Jonathan et al. (2016) Finite Element Modeling of Mitral Valve Repair. J Biomech Eng 138:021009
Morgan, Ashley E; Pantoja, Joe L; Grossi, Eugene A et al. (2016) Neochord placement versus triangular resection in mitral valve repair: A finite element model. J Surg Res 206:98-105
Purvine, Emilie; Monson, Kyle; Jurrus, Elizabeth et al. (2016) Energy Minimization of Discrete Protein Titration State Models Using Graph Theory. J Phys Chem B 120:8354-60
Bucero, Marta Abril; Bajaj, Chandrajit; Mourrain, Bernard (2016) On the construction of general cubature formula by flat extensions. Linear Algebra Appl 502:104-125
Ebeida, Mohamed S; Rushdi, Ahmad A; Awad, Muhammad A et al. (2016) Disk Density Tuning of a Maximal Random Packing. Comput Graph Forum 35:259-269
Yang, Pei-Chi; Boras, Britton W; Jeng, Mao-Tsuen et al. (2016) A Computational Modeling and Simulation Approach to Investigate Mechanisms of Subcellular cAMP Compartmentation. PLoS Comput Biol 12:e1005005
Watson, Shana R; Liu, Piaomu; Peña, Edsel A et al. (2016) Comparison of Aortic Collagen Fiber Angle Distribution in Mouse Models of Atherosclerosis Using Second-Harmonic Generation (SHG) Microscopy. Microsc Microanal 22:55-62

Showing the most recent 10 out of 270 publications