Dr. Aleksandra Trifunovic

Organisation / Institute
CECAD at the Institute for Genetics
Zülpicher Str.47a
50674 Köln

Address

Dr.Aleksandra Trifunovic
CECAD at the Institute for Genetics
Zülpicher Str.47a
50674 Köln

aleksandra.trifunovic[at]uk-koeln.de

 

 

PD Dr. Volker Rudolph

Organisation / Institute
Department III of Internal Medicine
Cologne University Heart Center

Address

PD Dr. Volker Rudolph
Department III of Internal Medicine,
Cologne University Heart Center
Kerpener Str. 62
50937 Köln, Germany

volker.rudolph[at]uk-koeln.de  

Dr. Aleksandra Trifunovic / Dr. Volker Rudolph

Project description:

The role of mitochondrial respiratory chain and oxidative phosphorylation (OXPHOS) in vascular system

Aleksandra Trifunovic / Volker Rudolph

Aims: Mitochondrial dysfunction is part of both normal and premature ageing, and can contribute to inflammation, cell senescence and apoptosis. Increasing evidence indicates that mitochondrial damage and dysfunction also occur in vascular diseases, in particular atherosclerosis, and may contribute to the multiple pathological processes underlying the disease. The vascular endothelium or smooth muscle cells (VSMC) are relatively independent of mitochondrial energy generating oxidative pathways, therefore mitochondria function in these cells have been somewhat neglected. Nevertheless, both cell types have an extensive mitochondrial network, suggesting that mitochondrial function may be important in response to stress and signalling in these cells. Using mouse models, in which mitochondrial protein synthesis and hence oxidative phosphorylation is dirupted in endothelial and vascular smooth muscle, respectively, this project plans to shed more light on the role of mitochondrial function in these two cell types and critically evaluate the role of mitochondrial function in vascular disease.

 

 

General research interest of the group:

Mitochondria are the main energy producing stations within our cells. Over three decades ago Hartman was one of the first to propose that mitochondria play a central role in ageing. The initial theory suggested that ageing, as well as the associated degenerative diseases, could be attributed to the deleterious effects of reactive oxygen species (ROS) on various cell compartments. The fact that the mitochondrial electron transport chain is the major site of production of reactive oxygen species has lead to the suggestion that mitochondria are a prime target for oxidative damage and hence the mitochondrial theory of ageing, a correlate of the free radical theory. This idea is intellectually very appealing, as mitochondria are the only organelles in animal cells that possess their own DNA, mtDNA, localized in the physical proximity to the respiratory chain, allowing irreversible damage to be introduced. The mitochondrial theory of ageing is based around the idea that mitochondrial DNA (mtDNA) mutations accumulate progressively during life and are directly responsible for a respiratory chain dysfunction that leads to an impaired bioenergetic homeostasis and an enhanced production of free oxygen radicals.

Recently, we have made a considerable progress in understanding basic role of acquired mtDNA mutations in ageing by generating the mtDNA mutator mice. The creation of mtDNA-mutator mice has provided the first direct evidence that accelerating mtDNA mutation rate can result in premature ageing, consistent with the view that loss of mitochondrial function is a major causal factor in ageing. Furthermore, we showed that there is no direct connection between increased mtDNA mutation load and elevated ROS production, arguing against a direct role of oxidative stress in the ageing process.

The main focus of our group is to understand the role of mitochondrial (dys)function in the determination of longevity. We are also interested in understanding molecular mechanisms by which mitochondria contribute to development and progression of age-associated diseases. We are studying these complex aspects of mitochondrial biology using two different model systems: transgenic mice and a roundworm, Caenorhabditis elegans.

 

 

PI Profile Aleksandra Trifunovic

Date of birth            May 19, 1971

Address                   CECAD at the Institute for Genetics
                              University of Cologne
                              Zülpicher Str. 47a, 50674 Cologne

                              E-mail:           aleksandra.trifunovic@uk-koeln.de

Position                   Independent Group Leader

Education

1989-1994               BSc in Biology, Faculty of Biology, University of Belgrade, Yugoslavia

1994-1998               Magister in Molecular Biology and Biochemistry at 
                               the Institute of Molecular Genetics and Genetic Engineering 
                               (IMGGE), University of Belgrade, Yugoslavia

1998-2000               PhD in Molecular Biology and Biochemistry at IMGGE, 
                               University of Belgrade, Yugoslavia

Research Career    

2009 - 2014               Independent Research Group Leader on Tenure track at the 
                                 Cologne Excellence Cluster: Cellular Stress responses 
                                 in Aging-Associated Diseases (CECAD), 
                                 University of Cologne, Germany

2006-2011                 Independent Junior Group Leader/Assistant Professor -
                                 position financed by Swedish Research Counsel. The
                                 position was located at the Department of Laboratory
                                 Medicine, Karolinska Institute, Stockholm, Sweden

2005-2006                 Research Assistant, financed by fellowship from Loo and
                                 Hans Ostermans Stiftelse. The position was located at the 
                                 Department of Laboratory Medicine, Karolinska Institute,
                                 Stockholm, Sweden.

2000 –2005               Postdoctoral fellow, laboratory of Prof Nils-Göran Larsson, 
                                 Department of Molecular Medicine and Department of
                                 Medical Nutrition, Karolinska Institute, Stockholm, Sweden

Service to Scientific Community and Honours

Since 2012                       Visiting Professor, Medical School, Belgrade University, 
                                       Serbia

Since 2011                       Editorial board member Frontiers in Science

Since 2010                       Member of the Scientific Committee for 8th and 9th
                                       European Meeting on Mitochondrial Pathology

Since 2008                       Member of the Organizing Committee for FEBS/EMBO
                                       Course Mitochondria in life, death and disease 

2007                                Young Investigator award Jaensson Foundation

 

Selected Publications

Pujol C, Bratic-Hench I, Sumakovic M, Hench J, Mourier A, Baumann L, Pavlenko V, Trifunovic A. Succinate Dehydrogenase Upregulation Destabilize Complex I and Limits the Lifespan of gas-1 Mutant. PLoS One. (2013); 8(3):e59493.

Ahlqvist K, Uutela M, Terzioglu M, Götz A, Salven P, Angers-Loustau A, Kopra OH, Hämäläinen RH, Tyynismaa H, Larsson NG, Kirmo W, Prolla T, Trifunovic A, Suomalainen A. (2012) Somatic stem cell homeostasis disrupted by mitochondrial DNA mutagenesis in prematurely aging mice. Cell Metab. Jan 4;15(1):100-9.

Hench J, Bratić Hench I, Pujol C, Ipsen S, Brodesser S, Mourier A, Tolnay M, Frank S, Trifunović A. A tissue-specific approach to the analysis of metabolic changes in Caenorhabditis elegans. PLoS One. 2011;6(12):e28417. Epub 2011 Dec 5.

Ross JM, Öberg J, Brene S, Coppotelli G, Terzioglu M, Pernold K, Goiny M, Sitnikov R, Kehr J,  Trifunovic A, Larsson NG, Hoffer BJ, Olson L. High brain Lactate is a hallmerk of aging and caused by a shift in the lactate dehydrogenase A/B ratio. (2010) Proc Acad Natl Sci USA Nov 16;107(46):20087-92.

Edgar D, Shabalina I, Camara Y, Wredenberg A, Calvaruso MA, Nijtmans  L, Nedergaard J, Cannon B, Larsson NG,  Trifunovic A. (2009)  Random point mutations with major effects on protein coding genes drive premature ageing in mtDNA mutator mice. Cell Metab. Aug; (10):131-138.

Bratic I, Hench J, Henriksson J, Antebi A, Burglin T, Trifunovic A. (2009) Mitochondrial DNA levels, but not mitochondrial DNA polymerase, are essential for C. elegans development. Nucleic Acids Res. Apr;37(6):1817-28.

Stewart JB, Freyer C, Elson JL, Wredenberg A, Cansu Z, Trifunovic A, Larsson NG. (2008) Purifying selection in transmission of mammalian mitochondrial DNA. PLoS Biol  Jan;6(1):e10.

Ekstrand MI, Terzioglu M, Galter D, Zhu S, Hofstetter C, Lindqvist E, Trifunovic A, Hoffer B, Mohammed AH, Olson L, Larsson NG. (2007) Respiratory chain dysfunction in dopamine neurons causes key Parkinson´s disease pathology in mice. Proc Natl Acad Sci U S A. 23;104(4):1325-30. Epub 2007 Jan 16.

Trifunovic, A., Hansson, A., Wredenberg, A., Rovio, A., Dufour, E., Khvorostov, I., Spelbrink, J., Wibom, R., Jacobs, H., Larsson, NG. (2005) Somatic mtDNA mutations cause ageing phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci USA, 102, 17993-17998

Hance N, Ekstrand M, Trifunovic A. (2005) Mitochondrial DNA polymerase gamma is essential for mammalian embryogenesis. Hum Mol Genet. 14 (13); 1775-1783.

Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlof S, Oldfors A, Wibom R, Tornell J, Jacobs HT, Larsson NG. (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. May 27;429 (6990):417-23.

Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM. (2002) Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat Genet. Jul; 31 (3):289-94.