The key role of cytochrome c in apoptosis is widely accepted. However, the requirement of cytochrome c for apoptosome formation has been defined mostly by in vitro assays. In vivo, cytochrome c translocation from the mitochondria to the cytosol is an indicator of apoptosis, but this association does not address the actual mechanism, requirements and the sequence of events leading to apoptosis. Proof of cytochrome c requirement for in vivo apoptosis has been hampered by the lack of mutants and its dual role. In addition, we and others have also shown that defects in oxidative phosphorylation can protect cells from an apoptotic death Therefore, it is important to differentiate the oxidative phosphorylation effect from the apoptosome assembly catalysis role of cytochrome c. To better define the mechanisms associated with the intrinsic apoptotic mechanism (the mitochondrial pathway), we propose to develop and analyze cytochrome c deficient cells and mice These studies have far reaching implications to different areas of medical and biological research, including cancer, neurodegeneration and development.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA085700-09
Application #
7748925
Study Section
Tumor Progression and Metastasis Study Section (TPM)
Program Officer
Salnikow, Konstantin
Project Start
2000-04-01
Project End
2011-12-31
Budget Start
2010-01-01
Budget End
2011-12-31
Support Year
9
Fiscal Year
2010
Total Cost
$242,663
Indirect Cost
Name
University of Miami School of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
(2015) Retraction Notice to: mTERF2 Regulates Oxidative Phosphorylation by Modulating mtDNA Transcription. Cell Metab 22:751
Wang, Xiao; Peralta, Susana; Moraes, Carlos T (2013) Mitochondrial alterations during carcinogenesis: a review of metabolic transformation and targets for anticancer treatments. Adv Cancer Res 119:127-60
Diaz, Francisca; Enriquez, Jose Antonio; Moraes, Carlos T (2012) Cells lacking Rieske iron-sulfur protein have a reactive oxygen species-associated decrease in respiratory complexes I and IV. Mol Cell Biol 32:415-29
Peralta, Susana; Wang, Xiao; Moraes, Carlos T (2012) Mitochondrial transcription: lessons from mouse models. Biochim Biophys Acta 1819:961-9
Dillon, Lloye M; Rebelo, Adriana P; Moraes, Carlos T (2012) The role of PGC-1 coactivators in aging skeletal muscle and heart. IUBMB Life 64:231-41
Wenz, Tina; Wang, Xiao; Marini, Matteo et al. (2011) A metabolic shift induced by a PPAR panagonist markedly reduces the effects of pathogenic mitochondrial tRNA mutations. J Cell Mol Med 15:2317-25
Rebelo, Adriana P; Dillon, Lloye M; Moraes, Carlos T (2011) Mitochondrial DNA transcription regulation and nucleoid organization. J Inherit Metab Dis 34:941-51
Diaz, Francisca; Kotarsky, Heike; Fellman, Vineta et al. (2011) Mitochondrial disorders caused by mutations in respiratory chain assembly factors. Semin Fetal Neonatal Med 16:197-204
Wang, Xiao; Moraes, Carlos T (2011) Increases in mitochondrial biogenesis impair carcinogenesis at multiple levels. Mol Oncol 5:399-409
Wenz, Tina; Williams, Sion L; Bacman, Sandra R et al. (2010) Emerging therapeutic approaches to mitochondrial diseases. Dev Disabil Res Rev 16:219-29

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