Abstract

The overall objective of this project is to gain a greater understanding of the factors which regulate mitochondrial biogenesis. Although mitochondria have the ability to synthesize less than 10% of their total proteins, the 8-10 hydrophobic proteins made within the mitochondria are essential for the formation of a functional respiratory chain and ATP synthesizing complex. This project proposes to investigate the mechanisms wwhich control the synthesis of mitochondrial proteins at the two different intracellular sites. Specifically possible controls at the two different transcriptional and translational level will be investigated by the use of polysomes isolated from yeast mitochondria. Mitochondrial messenger RNAs will be characterized as will be the nature of the nascent chains present on the polysomes. In conjunction with these studies, the assembly of cytochrome b, a proposed product of mitochondrial protein synthesis, into complex III of the respiratory chain will be studied by use of specific mutants as well as antibodies to the purified enzyme. These proposed experiments should help elucidate how the mitochondrial membrane is assembled.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM038433-03
Application #
3294857
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1985-09-01
Project End
1991-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
West Virginia University
Department
Type
School of Medicine & Dentistry
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506

  Publications

Wang, Y; Bruel, C; Yan, L et al. (1998) Exogenous ubiquinol analogues affect the fluorescence of NCD-4 bound to aspartate-160 of yeast cytochrome b. J Bioenerg Biomembr 30:455-64
Obungu, V H; Wang, Y; Beattie, D S (1998) The role of charged amino acids in the alpha1-beta4 loop of the iron-sulfur protein of the cytochrome bc1 complex of yeast mitochondria. J Biol Chem 273:11917-22
Wang, Y; Obungu, V; Beattie, D S (1998) Dicyclohexylcarbodiimide inhibits proton pumping in ubiquinol:cytochrome c oxidoreductase of Rhodobacter sphaeroides and binds to aspartate-187 of cytochrome b. Arch Biochem Biophys 352:193-8
Obungu, V; Yu, L P; Japa, S et al. (1997) The role of the membrane-spanning and extra-membranous regions of the iron-sulfur protein in its assembly into the cytochrome bc1 complex of yeast mitochondria. Biochim Biophys Acta 1321:229-37
Ramabadran, R S; Japa, S; Beattie, D S (1997) Assembly of deletion mutants of the Rieske iron-sulfur protein into the cytochrome bc1 complex of yeast mitochondria. J Bioenerg Biomembr 29:45-54
Beattie, D S; Howton, M M (1996) The presence of rotenone-sensitive NADH dehydrogenase in the long slender bloodstream and the procyclic forms of Trypanosoma brucei brucei. Eur J Biochem 241:888-94
Wang, Y; Howton, M M; Beattie, D S (1995) Topographical organization of cytochrome b in the yeast mitochondrial membrane determined by fluorescence studies with N-cyclohexyl-N'-[4-(dimethylamino)naphthyl]carbodiimide. Biochemistry 34:7476-82
Japa, S; Sun, J Z; Beattie, D S (1995) Import of subunit VII of the cytochrome bc1 complex into yeast mitochondrial. Arch Biochem Biophys 319:250-6
Japa, S; Beattie, D S (1994) Sequences of the iron-sulfur protein precursor necessary for its import and two-step processing in yeast mitochondria. Arch Biochem Biophys 312:414-20
Beattie, D S; Obungu, V H; Kiaira, J K (1994) Oxidation of NADH by a rotenone and antimycin-sensitive pathway in the mitochondrion of procyclic Trypanosoma brucei brucei. Mol Biochem Parasitol 64:87-94

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