The investigator has developed a novel cell -free system based on extracts from eggs of the frog, Xenopus laevis. Such egg extracts are able to reproduce many of the features of apoptosis, including chromatin condensation, endonucleolytic DNA cleavage and the shrinkage and fragmentation of the nuclei. Lysates from baculovirus-infected cells expression the oncogene bcl-2 can suppress nuclear fragmentation. This system provides an excellent means to dissect the molecular mechanisms of apoptosis and protective function of bcl-2. The applicant proposes to identify and characterize some of the cytoplasmic events of apoptosis. Such cell-free systems offer the opportunity to reconstitute the apoptotic process from fractionated components.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050284-03
Application #
2857189
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1997-01-01
Project End
2000-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
La Jolla Institute
Department
Type
DUNS #
603880287
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Kushnareva, Y; Seong, Y; Andreyev, A Y et al. (2016) Mitochondrial dysfunction in an Opa1(Q285STOP) mouse model of dominant optic atrophy results from Opa1 haploinsufficiency. Cell Death Dis 7:e2309
Kushnareva, Yulia; Andreyev, Alexander Y; Kuwana, Tomomi et al. (2012) Bax activation initiates the assembly of a multimeric catalyst that facilitates Bax pore formation in mitochondrial outer membranes. PLoS Biol 10:e1001394
Kushnareva, Yulia; Newmeyer, Donald D (2010) Bioenergetics and cell death. Ann N Y Acad Sci 1201:50-7
Lartigue, Lydia; Kushnareva, Yulia; Seong, Youngmo et al. (2009) Caspase-independent mitochondrial cell death results from loss of respiration, not cytotoxic protein release. Mol Biol Cell 20:4871-84
Yamaguchi, Ryuji; Lartigue, Lydia; Perkins, Guy et al. (2008) Opa1-mediated cristae opening is Bax/Bak and BH3 dependent, required for apoptosis, and independent of Bak oligomerization. Mol Cell 31:557-69