This aim of this research project is to elucidate the mechanism by which the small Tim (translocase of the inner membrane) proteins of the mitochondrial inner membrane space interact with each other and with their substrate proteins. The small, soluble Tim proteins (Tim8p, Tim9p, Tim10p, Tim12p, and Tim13p) share a conserved amino acid structure described as a """"""""twin CX3C"""""""" motif, which has been identified as a possible site of disulfide bond formation. The presence and importance of disulfide bond formation to the structure and function of the small Tim proteins will be determined. Additionally, novel pathways in S. cerevisiae that are affected by the redox state of the cell will be identified. By varying the concentration of oxidizing and reducing agents, a screen of the S. cerevisiae deletion library can identify hypo- and hypersensitive redox mutants. The genes identified will be characterized biochemically and genetically to determine their role in cellular redox homeostasis. Also screened will be S. cerevisiae temperature sensitive mutants of the tim9, tim10, tim12, and tim22 alleles, all components of inner membrane translocation. Mitochondrial protein translocation is of enormous interest since the association of diseases to import dysfunction was established.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31GM070415-01
Application #
6745790
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Toliver, Adolphus
Project Start
2003-12-01
Project End
2008-11-30
Budget Start
2003-12-01
Budget End
2004-11-30
Support Year
1
Fiscal Year
2003
Total Cost
$27,708
Indirect Cost
Name
University of California Los Angeles
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Koehler, Carla M; Beverly, Kristen N; Leverich, Edward P (2006) Redox pathways of the mitochondrion. Antioxid Redox Signal 8:813-22
Curran, Sean P; Leverich, Edward P; Koehler, Carla M et al. (2004) Defective mitochondrial protein translocation precludes normal Caenorhabditis elegans development. J Biol Chem 279:54655-62
Curran, Sean P; Leuenberger, Danielle; Leverich, Edward P et al. (2004) The role of Hot13p and redox chemistry in the mitochondrial TIM22 import pathway. J Biol Chem 279:43744-51