B.Sc. 1984, University College, Dublin, Ireland
M.Sc. 1985, University College, Dublin, Ireland
Dr. rer. nat. 1989, Ludwig-Maximillians Universität, München, Germany
Postdoctoral position: Imperial Cancer Research Fund, London, U.K.
Dr. rer. biol. hum. Habil. 1998, Ludwig-Maximillians Universität, München, Germany
Mitochondrial Biogenesis using Yeast as a Model Organism
Mitochondria play a pivotal role in the life of cells, controlling diverse processes ranging from energy production to ion homoeostasis, heme, lipid and amino acid biosynthesis and the regulation of cell death. In humans, numerous pathological conditions have been linked to mitochondrial dysfunction and defects in their oxidative phosphorylation (OXPHOS) capacity. The activity of the mitochondrial respiratory chain protein complexes is primarily or secondarily affected in OXPHOS metabolism diseases, which in turn leads to impaired oxygen utilization, reduced energy (ATP) production and generation of oxidative stress conditions leading to the production of reactive oxygen species (ROS). The research in my laboratory is focused on understanding the protein composition and process of assembly of the mitochondrial respiratory chain (OXPHOS) complexes. The OXPHOS complexes are large multi-subunit complexes that are embedded in the inner mitochondrial membrane. The majority of the proteins contained within these complexes are encoded in the cell’s nucleus and are imported into the mitochondria. A few of the subunits of respiratory chain complexes are encoded by the mitochondrial genome and are synthesized within the matrix compartment. Our current research is focused on two aspects of the assembly process, (i) the synthesis and sorting of mitochondrially encoded proteins into the inner membrane by a process which is mediated by the Oxa1 protein complex; and (ii) the assembly and function of the supercomplex assembly states of the mitochondrial oxidative phosphorylation machinery. We primarily use the yeast Saccharomyces cerevisiae as a model system and are adopting a variety of genetic and biochemical approaches. The relative simplicity of this single-celled organism, its amenity to easy genetic manipulation and the fact that it can live by anaerobic fermentation, has allowed us to identify and assign roles to individual genes in the process of OXPHOS complex assembly and function. Our understanding of the workings of the individual OXPHOS complexes, at the enzymatic and regulatory level, has been advanced by the ability to purify the individual enzymes and thus enabling the analysis of their protein composition.
Selected Publications
Kaur, J., and Stuart, R.A. 2011. Truncation of the Mrp20 protein reveals a novel ribosome assembly subcomplex in mitochondria. EMBO Reports, in press.
Stuart, R.A. 2009. Supercomplex organization of the yeast respiratory chain complexes and the ADP/ATP carrier proteins. Methods Enzymol. 456:191-208.
Stuart, R.A. 2009. Supercomplex organization of the oxidative phosphorylation enzymes in yeast mitochondria. J. Bioenerg. Biomembr, 40:411-417.
Jia, L., Kaur, J. and Stuart, R.A. 2009. Mapping the yeast Oxa1-mitochondrial ribosome interface: identification of MrpL40, a ribosomal protein in close proximity to Oxa1 and critical for OXPHOS complex assembly. Eukaryot. Cell, 11:1792-1802.
Wittig, I, Velours, J., Stuart, R.A. and Schägger, H. 2008. Characterization of domain interfaces in monomeric and dimeric ATP synthase. Mol. Cell. Proteomics, 7:995-1004.
Yao, H., Stuart, R.A., Cai, S. and Sem, D. 2008. Structural characterization of the transmembrane domain from subunit e (Su e) of yeast F1Fo-ATP synthase: a helical GXXXG motif located just under the micelle surface. Biochemistry, 47:1910-1917.
Saddar, S. Dienhart, M.K., and Stuart, R.A. 2008. The F1Fo-ATP synthase complex influences the assembly state of the cytochrome bc1-cytochrome oxidase supercomplex and its association with the TIM23 machinery. J. Biol. Chem., 283:6677-6686.
Dienhart, M.K. and Stuart, R.A. 2008. The yeast Aac2 protein exists in physical association with the cytochrome bc1-COX supercomplex and the TIM23 machinery. Mol. Biol. Cell., 19:3934-3943.
Jia, L., Dienhart, M.K. and R.A. Stuart. 2007. Oxa1 directly interacts with Atp9 and mediates its assembly into the mitochondria F1Fo-ATP synthase complex. Mol. Biol. Cell., 18:1897-1908.
Undergraduate Students |
Graduate Students |
Research Associate |
| Jasvinder Kaur | Vera Strogolova | |
| Joshua Garlich | ||
| Sneha Potdar |
Recent Past Members
Dr. Valerie Everard-Gigot
Dr. Sonika Saddar
Dr. Lixia Jia
Dr. Sherrea Herod
Dr. Mary Dienhart
Jeremy Bushman
Andrew Furness
Micaela Robb-McGrath
Biological Sciences Department
Marquette University, Wehr Life Sciences
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P.O. Box 1881
Milwaukee, WI 53201-1881
(414) 288-7355
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