Laboratory of Mitochondrial Biogenesis
(since November 2009)

Head: Post-doctoral fellows:   PhD students: Research Assistant: Undergraduate students:

Agnieszka Chacinska, PhD Magdalena Kaus-Drobek, PhD Adrianna Loniewska-Lwowska, PhD Piotr Bragoszewski, PhD Malgorzata Sztolsztener, PhD Tomasz Czerwik, MSc Agnieszka Gornicka, MSc Aksana Varabyova, MSc Lidia Wrobel, MSc Anita Chodkowska, MSc Paulina Kwiatkowska, Inmaculada Mora Espi, Kamila Ornoch

Agnieszka Chacińska's profile in Science:
http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2010_03_19/caredit.a1000027

Curriculum Vitae
Agnieszka Chacinska

Brief review of scientific interests and achievements:

My scientific interests have been oscillating around the fundamental questions of cell biology related to organellar and protein biogenesis. The findings of my PhD thesis (laboratory of Prof. Magdalena Boguta) provided an insight into the functional implications of self-perpetuating conformational changes within proteins (prions). During the post-doctoral training, I had worked with Prof. Nikolaus Pfanner, a world-class specialist in the field of protein import into mitochondria. Initially, I pursued a longstanding question on the communication between the outer and inner mitochondrial membranes during protein transport. At that time, mitochondrial protein translocons were believed to be rather static machines. Challenging this view, my and others work revealed an amazing dynamics and flexibility of membrane complexes responsible for the recognition, transfer and sorting of mitochondrial proteins, and thereby substantially contributed to the current understanding of the mechanisms responsible for the protein translocation across biological membranes.

At a later stage of post-doc, I made a surprising discovery that ruled out the dogma on the absence of disulfide bonds in reducing cellular compartments such as mitochondria. The identification of Mia40, the first component in a novel protein import pathway that relies on the transfer of disulfide bonds, opened new research theme in cell biology for our group. We have continued the fascinating and competitive studies on the MIA pathway with important implications for the biogenesis, folding and sorting of proteins in the cell. Our future research, supported by the Welcome grant from the Foundation for Polish Science, EMBO Installation grant and the grant from Ministery of Science in Poland, will explore novel and exciting links between disulfide bond formation mechanisms and mitochondrial protein homeostasis.

Chacinska, A., Koehler, C.M., Milenkovic, D., Lithgow, T., Pfanner, N. (2009) Importing mitochondrial proteins: machineries and mechanisms. Cell 138, 628-644.

Chacinska, A., Pfannschmidt, S., Wiedemann, N., Kozjak, V., Sanjuán Szklarz, L.K., Schulze-Specking, A., Truscott, K.N., Guiard, B., Meisinger, C., and Pfanner, N. (2004). Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins. EMBO J. 23, 3735-3746.

Chacinska, A.*, Lind, M.*, Frazier, A.E., Dudek, J., Meisinger, C., Geissler, A., Sickmann, A., Meyer, H.E., Truscott, K.N., Guiard, B., Pfanner, N., and Rehling, P. (2005). Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell 120, 817-829 (*equal contribution).

Rissler, M., Wiedemann, N., Pfannschmidt, S., Gabriel, K., Guiard, B., Pfanner, N., and Chacinska, A. (2005). The essential mitochondrial protein Erv1 cooperates with Mia40 in biogenesis of intermembrane space proteins. J. Mol. Biol. 353, 485-492.

Milenkovic, D., Gabriel, K., Guiard, B., Schulze-Specking, A., Pfanner, N., Chacinska, A (2007) Biogenesis of the essential Tim9-Tim10 chaperone complex of mitochondria: site-specific recognition of cysteine residues by the intermemembrane space receptor Mia40. J. Biol. Chem. 282, 22472-22480.

Müller, J.M., Milenkovic, D., Guiard, B., Pfanner, N., Chacinska A. (2008) Precursor oxidation by Mia40 and Erv1 promotes vectorial transport of proteins into the mitochondrial intermembrane space. Mol. Biol Cell 19, 226-236.

Chacinska*, A., Guiard*, B., Müller, J.M., Schulze-Specking, A., Gabriel, K., Kutik S., Pfanner N. (2008) Mitochondrial biogenesis: switching the sorting pathways of the intermembrane space receptor Mia40. J. Biol. Chem. 283, 29723-29729. (*equal contribution).

Stojanovski, D., Milenkovic, D., Müller, J.M., Gabriel, K., Schulze-Specking, A., Baker, M.J., Ryan, M.T., Guiard, B., Pfanner, N., Chacinska, A. (2008) Mitochondrial protein import: precursor oxidation in a ternary complex with disulfide carrier and sulfhydryl oxidase. J. Cell Biol. 183, 195-202.

Milenkovic, D., Ramming, T., Müller, J.M., Wenz L.S., Gebert, N., Schulze-Specking, A., Stojanovski, D., Rospert, S., Chacinska, A. (2009) Identification of the signal directing Tim9 and Tim10 into the intermembrane space of mitochondria. Mol. Biol. Cell 20, 2530-2539.

All publications afiliated to Institute for Biochemistry and Molecular Biology, University of Freiburg