ACTIVATION OF MITOCHONDRIAL OUTER MEMBRANE PERMEABILIZATION BY BH3-ONL

BH3-ONL 激活线粒体外膜透化

• 批准号: 7957616
• 负责人: DONALD DAVID NEWMEYER
• 金额: $ 0.94万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7957616
• 关键词: ATP Synthesis Pathway; Aging; Animals; Apoptosis; Biogenesis; Computer Retrieval of Information on Scientific Projects Database; Crista ampullaris; Development; Electron Microscope; Funding; Grant; Image Analysis; Institution; Membrane; Mitochondria; Outer Mitochondrial Membrane; Play; Reaction; Research; Research Personnel; Resources; Role; Source; Tissues; United States National Institutes of Health; crista membrane; cytochrome c; meetings; tomography

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Since the intercellular energy needs are different from tissue to tissue, sometimes demands made on mitochondria for more energy must be met by creating more cristae membrane in each mitochondrion where ATP synthesis take place. Thus the biogenesis of mitochondrial cristal membrane plays an important role both in development and in aging of animals. Recent evidence suggests that Opa1 is critical in regulating the crista junction size and the accessibility of the intracristal space. During apoptosis, Opa1 oligomers are disassembled and accessibility of cytochrome c in the intracristal space increases dramatically. Several years ago, this observation led Scorrano and colleagues to suggest that crista junctions become wider during apoptosis, releasing cytochrome c from intracristal spaces. As roughly 85% of total mitochondrial cytochrome c resides within intracristal spaces that are connected to the IMS by relatively narrow crista junctions, it has been suggested that the remodeling of cristae and crista junctions is a required step in the rapid and complete release of cytochrome c. N/C-Bid-induced structural changes in cristae and crista junctions are also suggested by observations of increased accessibility of cytochrome c to reaction partners at the outer membrane. However, the role of crista remodeling in apoptosis is controversial. Hence we are using electron microscope tomography to characterize when remodeling occurs and when it doesn't as a function of treatment with proapoptotic effectors and compounds that disassemble Opa1 oligomers.

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