Most of the ATP used for the different work performances of eucaryotic cells is derived from the metabolic pathways housed in mitochondria. This ancient organelle, believed to be a descendant of an earlier aerobic procaryote, has retained only a vestige of its original genetic information, most having been transferred to the nucleus of the host cell. The maintenance of functinal mitochondria in yeast and higher eucaryotic cells is governed by 30-40 genes resident in mitochondrial DNA and approximately 300 genes located in chromosomal DNA. Several large scale screens for respiratory defective strains of the yeast Saccharomyces cerevisiae, were carried out in prior grant periods. The mutants, comprising some 215 complementation groups, describe a wide range of different functions essential for expression of respiratory competent mitochondria. Most of the genes represented by the mutants have been cloned and sequenced. In many instances, the functions of the encoded products have been identified. Several goals will be pursued during the coming period. The assembly of the ATPase and bc1 complexes will be analyzed by both traditional biochemical methods and through studies aimed at gaining a more precise understanding of the functions carried out by novel gene products that affect late events in the assembly pathway. The second goal is to make use of the genes for the mitochondrial ribosomal proteins and aminoacyl-tRNA synthetases to clarify issues related to the regulation and evolution of these mitochondrial constituents. Finally, the analysis of the mutants collection will be completed. Hopefully, this will provide a genetic blueprint of mitochondrial morphogenesis and answer some of the still outstanding questions regarding the mechanisms insuring their continuity during cell growth and division.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Physical Biochemistry Study Section (PB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Columbia University (N.Y.)
Other Domestic Higher Education
New York
United States
Zip Code
Barros, Mario H; Tzagoloff, Alexander (2017) Aep3p-dependent translation of yeast mitochondrial ATP8. Mol Biol Cell 28:1426-1434
Rak, Malgorzata; Su, Chen Hsien; Xu, Jonathan Tong et al. (2016) Regulation of mitochondrial translation of the ATP8/ATP6 mRNA by Smt1p. Mol Biol Cell 27:919-29
Schiff, Manuel; Veauville-Merllié, Alice; Su, Chen Hsien et al. (2016) SLC25A32 Mutations and Riboflavin-Responsive Exercise Intolerance. N Engl J Med 374:795-7
Su, Chen-Hsien; McStay, Gavin P; Tzagoloff, Alexander (2014) Assembly of the rotor component of yeast mitochondrial ATP synthase is enhanced when Atp9p is supplied by Atp9p-Cox6p complexes. J Biol Chem 289:31605-16
Gaignard, Pauline; Menezes, Minal; Schiff, Manuel et al. (2013) Mutations in CYC1, encoding cytochrome c1 subunit of respiratory chain complex III, cause insulin-responsive hyperglycemia. Am J Hum Genet 93:384-9
Paul, Marie-Françoise; Alushin, Gregory M; Barros, Mario H et al. (2012) The putative GTPase encoded by MTG3 functions in a novel pathway for regulating assembly of the small subunit of yeast mitochondrial ribosomes. J Biol Chem 287:24346-55
Barros, Mario H; Rak, Malgorzata; Paulela, Janaina A et al. (2011) Characterization of Gtf1p, the connector subunit of yeast mitochondrial tRNA-dependent amidotransferase. J Biol Chem 286:32937-47
Rak, Malgorzata; Gokova, Samanta; Tzagoloff, Alexander (2011) Modular assembly of yeast mitochondrial ATP synthase. EMBO J 30:920-30
Rak, Malgorzata; McStay, Gavin P; Fujikawa, Makoto et al. (2011) Turnover of ATP synthase subunits in F1-depleted HeLa and yeast cells. FEBS Lett 585:2582-6
Busso, Cleverson; Tahara, Erich B; Ogusucu, Renata et al. (2010) Saccharomyces cerevisiae coq10 null mutants are responsive to antimycin A. FEBS J 277:4530-8

Showing the most recent 10 out of 53 publications