Dr. Rosemary Stuart

Dr. Rosemary Stuart
Dr. Rosemary StuartMarquette University

Wehr Life Sciences, 309

MilwaukeeWI53201United States of America
(414) 288-1472

Professor

Biogenesis and regulation of OXPHOS complexes

MU4Gold Scholars, Director

Publications

Education

B.Sc., 1984, University College, Dublin, Ireland
M.Sc., 1985, University College, Dublin, Ireland
Dr. rer. nat., 1989, Ludwig-Maximillians Universität, München, Germany
Postdoctoral Fellow, Imperial Cancer Research Fund, London, U.K.
Dr. rer. biol. hum. Habil., 1998, Ludwig-Maximillians Universität, München, Germany

Research Interests

Mitochondrial Biogenesis using Yeast as a Model Organism - Introduction

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. The research in our laboratory is focused on understanding the process of assembly and regulation of the mitochondrial OXPHOS complexes.

 

Project #1 The Central Protuberance Region of the Yeast Mitoribosome and its Role in Regulating OXPHOS Complex Biogenesis (NSF Funded)

Stuart ResearchA small, but enzymatically important, subset of OXPHOS proteins are encoded on the mitochondrial genome and synthesized by mitochondrial ribosomes (mitoribosomes). Our research seeks to understand the molecular mechanisms that regulate mitoribosome activity, and thus has important implications for the OXPHOS complex assembly and the bioenergetic capacity of the cell. The project is funded through the NSF is focused on the molecular dissection of the mitospecific protein MrpL35 (mL38) and partner proteins, Mrp7 (bL27) and MrpL28 (mL40). These proteins are located in the central protuberance (CP) region of the yeast mitoribosomal large subunit (54S subunit). Stuart ResearchOur lab’s recent findings have highlighted the CP as a key regulatory region of the mitoribosome, which serves to ensure coordination of the translational process with the downstream, chaperoned events of OXPHOS complex assembly, in particular of the cytochrome c oxidase (COX) enzyme (Box et al., 2017). We are currently pursuing experiments to gain a greater molecular and functional insight into these three key proteins and their interaction with each other.

 

Project #2: The HIG1 proteins and their association the cytochrome c oxidase complex (NIH funded)

The yeast mitochondrial proteins Rcf1 and Rcf2 are found in association with a subpopulation of the cytochrome bc1-cytochrome c oxidase (COX) complex and our findings support that they play a role in the assembly and/or modulating the activity of the COX enzyme (Strogolova et al., 2012, Garlich et al., 2017). Yeast Rcf1/Rcf2 proteins are members of the highly conserved Hig1 (hypoxia induced gene 1, Hig1) protein family found in alpha-proteobacteria and through to humans. Yeast mutants deficient in either Rcf1 or Rcf2 proteins retain their ability to grow through aerobic respiratory-based metabolism, whereas a strong growth defect is observed when both proteins are absent. Our current research project, funded by the NIH, seeks to explore the functional significance of the Rcf1 and Rcf2 proteins for supporting aerobic respiration, in particular the efficiency and coupling of the OXPHOS process. We are currently exploring the detrimental effects caused by the absence of Rcf1 and/or Rcf2, in particular on the ability the COX enzyme to maintain the proton motive force required to support the mitochondrial ATP synthesis process.

Selected Publications

  1. Strogolova, V., Hoang, N.H., Hosler, J and Stuart, R.A. 2019. The yeast mitochondrial proteins Rcf1 and Rcf2 support the enzymology of the cytochrome c oxidase complex and generation of the proton motive force. J. Biol. Chem. in press [Epub ahead of print]
  2. Box, J.M., Kaur, J., and Stuart, R.A. 2017. MrpL35, a mitospecific component of mitoribosomes, plays a key role in cytochromec oxidase assembly. Mol Biol Cell., 28:3489-3499
  3. Garlich, J., Strecker, V., Wittig, I., and Stuart, R.A. 2017. Mutational analysis of the QRRQ motif in the yeast Hig1-type 2 protein, Rcf1, reveals a regulatory role for the cytochrome c oxidase complex. Biol. Chem., 292:5216-5226.
  4. Strecker, V., Kadeer, Z., Heidler, J., Cruciat, C.M., Angerer, H., Giese, H., Pfeiffer, K., Stuart,A., and Wittig, I. 2016. Supercomplex-associated Cox26 protein binds to cytochrome c oxidase. Biochim Biophys Acta.1863:1643-52.
  1. Strogolova, V., Furness, A., Robb-McGrath, M., Garlich, J. and Stuart, R.A. 2012. Rcf1 and Rcf2, members of the hypoxia-induced gene 1 protein family, are critical components of the mitochondrial cytochrome bc1-cytochrome c oxidase supercomplex. Cell. Biol., 32:1363-73.
  2. Kaur, J., and Stuart, R.A. 2011. Truncation of the Mrp20 protein reveals a novel ribosome assembly subcomplex in mitochondria. EMBO Reports, 12:950-955.

Honors and Awards

Nora Finnigan Werra Faculty Achievement Award (2011)

Lawrence G. Haggerty Faculty Award for Research Excellence (2011)

Robert and Mary Gettel Faculty Award for Teaching Excellence (2008)

Lab Members

Current Lab Members
Dr. Vera Strogolova, Research Associate
Jodie Box, Research Associate
Maryrose Weatherton, Research Technician
Jessica Anderson (Ph.D. candidate)
Aidan Marick (undergraduate student)
Ana Paola (undergraduate student)

Previous Graduate Students at Marquette
Valerie Everard-Gigot, 2006, Ph.D.
Sonika Saddar, 2006, Ph.D
Lixia Jia, 2007, Ph.D.
Sherrea Herod, 2009, Ph.D.
Jasvinder Kaur, 2011, Ph.D.
Josh Garlich, 2016, Ph.D.
Vera Strogolova, 2018, Ph.D.


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Department of Biological Sciences

Wehr Life Sciences, 109
1428 W. Clybourn St.
Milwaukee, WI 53233

(414) 288-7355

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