Laboratory of Mitochondrial Biogenesis

Research interest

Mitochondria play a key role in metabolism and regulatory processes within a cell. Thus, the formation of mitochondria is essential for cellular function of every being in the eukaryotic kingdom, from unicellular organisms to mammals. Mitochondria comprise 1000-1500 cellular proteins, which are synthesized outside of the mitochondria in the cytosol.

The biogenesis of mitochondria relies on the efficient import, sorting, and maturation of proteins, all governed by conserved protein translocases and other complex biological machinery. We have identified a previously unknown mitochondrial intermembrane space assembly (MIA) pathway, which utilizes the transfer of disulfide bonds and is dedicated to the import and biogenesis of intermembrane space proteins, that lack a classical mitochondrial leader sequence.

Our research explores novel and exciting links between disulfide bond formation mechanisms and mitochondrial protein homeostasis. We postulate the presence of unique mechanisms involved in protein biogenesis that involve crosstalk between the cytosol and mitochondrial compartments. Our research addresses three major and related issues:

  1. Redox-related biogenesis events of mitochondrial proteins in yeast and higher eukaryotes;
  2. The impact of the MIA pathway on mitochondrial and cellular protein homeostasis;
  3. The biological consequences of oxidative protein biogenesis failure.

Our goal is to better understand the complex and dynamic processes involved in the formation of functional organelles, as well as the maintenance of mitochondrial protein homeostasis and its failures, which result in pathology.

We are always interested in highly motivated students and postdocs. Please enquire: a.chacinska@dev.dev.cent.uw.edu.pl/en  

Prof. Agnieszka Chacińska
email: a.chacinska@dev.dev.cent.uw.edu.pl/en
phone: +48 22 55 43639
room: 04.105
administration: Director

Education and degrees:
2014 Professor of Biological Sciences, nomination by the President of The Republic of Poland
2008 Dr hab., Institute of Biochemistry and Biophysics, Warsaw, Poland
1994-2000 PhD in Biochemistry, Institute of Biochemistry and Biophysics, Warsaw, Poland
1993 Master Degree in Molecular Biology, University of Warsaw
1988-1993 Study of Biology, University of Warsaw, Poland

Research experience and appointments:
since 10.2017 Director of “Regenerative Mechanisms for Health”, International Research Agenda Unit (“ReMedy”)
since 03.2017 Director of the Centre of New Technologies, University of Warsaw
since 10.2016 Visiting Professor at the University Medical Center Göttingen, Germany
2009-2017 Professor and Leader of the Laboratory of Mitochondrial Biogenesis at the International Institute of Molecular and Cell Biology in Warsaw, Poland
2015-2016 Deputy Director of Development at the International Institute of Molecular and Cell Biology in Warsaw, Poland
2008-2009 Associate Member of Excellence Cluster BIOSS–Centre for Biological Signalling Studies, University of Freiburg, Germany
2007-2010 Member of the Board, Collaborative Research Centre 746 (SFB 746), Germany
2007-2010 Project Leader in the Collaborative Research Centre 746 (SFB 746), Germany
2004-2009 Group Leader, Institute for Biochemistry and Molecular Biology, University of Freiburg, Germany
2001-2004 Postdoctoral Fellow in the laboratory of Prof. Nikolaus Pfanner, University of Freiburg, Germany
1999 Visiting scientist in the laboratory of Dr Sabine Rospert, Max Planck Research Unit, Halle, Germany
1996-1998 Visiting scientist in the laboratory of Prof. Gottfried Schatz, Biozentrum, University of Basel, Switzerland
1994-2000 Doctoral research with Prof. Magdalena Boguta, Institute of Biochemistry and Biophysics, Warsaw, Poland
Memberships and Awards:
2017 Leon Marchlewski Medal of The Committee on Molecular Biology of the Cell, Polish Academy of Science for outstanding contribution to the development of molecular biology, cell biology, biochemistry and biophysics
2017 Individual Award from the Rector of University of Warsaw
2016 Corresponding Member of the Polish Academy of Science
2016 Award from the Prime Minister of Poland for scientific achievements
2016 Elected EMBO member
2016 Laureate together with Peter Rehling of Nicolaus Copernicus Polish-German Research Award given jointly by the Foundation for Polish Science (FNP) and the German Research Foundation (DFG)
2015  Award from the Minister of Science and Higher Education for scientific achievements that led to the title of Professor
2015 Award from the President of Polish Academy of Science for scientific achievement
2009 Laureate of the Welcome Programme from the Foundation for Polish Science
2009 EMBO Installation Grantee
2008 Eugen-Graetz Prize for research, University of Freiburg
2001-2003 Long-term FEBS fellowship
2001 Award for the Ph. D. thesis, Institute of Biochemistry and Biophysics,
1997 Grant for young scientists from the Polish State Committee for Scientific Research
1996 Short-term FEBS fellowship


Publications without CeNT affiliation: 

  • Wasilewski, M., Chojnacka, K., Chacinska, A. (2017). Protein trafficking at the crossroads to mitochondria. Biochim Biophys Acta, 1864(1), 125-137.
  • Wasilewski, M., Chojnacka, K., Chacinska, A. (2016). Białka mitochondrialne – import, eksport, degradacja. Postępy Biochemii, 62(2), 94-102.
  • Callegari, S., Richter, F., Chojnacka, K., Jans, D.C., Lorenzi, I., Pacheu-Grau, D., Jakobs, S., Lenz, C., Urlaub, H., Dudek, J., Chacinska, A., Rehling, P. (2016). TIM29 is a subunit of the human carrier translocase required for protein transport. FEBS Lett, 590(23), 4147-4158.
  • Wrobel, L., Sokol, A.M., Chojnacka, M., and Chacinska, A. (2016). The presence of disulfide bonds reveals an evolutionarily conserved mechanism involved in mitochondrial protein translocase assembly. Sci Rep., 6, 27484.
  • Topf, U., Wrobel, L., and Chacinska, A. (2016). Chatty Mitochondria: Keeping Balance in Cellular Protein Homeostasis. Trends Cell Biol, 26(8), 577-86.
  • Turakhiya, U., von der Malsburg, K., Gold, V.A., Guiard, B., Chacinska, A., van der Laan, M., Ieva, R. (2016). Protein Import by the Mitochondrial Presequence Translocase in the Absence of a Membrane Potential. J Mol Biol, 428, 1041-52.
  • Wrobel, L., Topf, U., Bragoszewski, P., Wiese, S., Sztolsztener, M.E., Oeljeklaus, S., Varabyova, A., Lirski, M., Chroscicki, P., Mroczek, S., Januszewicz, E., Dziembowski, A., Koblowska, M., Warscheid, B., Chacinska, A. (2015). Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature, 524, 485-488.
  • Keatinge, M., Bui, H., Menke, A., Chen, Y.C., Sokol, A.M., Bai, Q., Ellett, F., Da Costa, M., Burke, D., Gegg, M., Trollope, L., Payne, T., McTighe, A., Mortiboys, H., de Jager, S., Nuthhall, H., Kuo, M.S., Fleming, A., Schapira, A.H., Renshaw, S.A., Highley, J.R., Chacinska, A., Panula, P., Burton, E.A., O’Neill, M.J., Bandmann, O. (2015). Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provise evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death. Hum Mol Genet, 24(23), 6640-52.
  • Sakowska P, Jans DC, Mohanraj K, Riedel D, Jakobs S, Chacinska A. The oxidation status of Mic19 regulates MICOS assembly. 2015. Mol Cell Biol, 35, 4222-4237.
  • Bragoszewski, P., Wasilewski, M., Sakowska, P., Gornicka, A., Böttinger, L., Qiu, J., Wiedemann, N., Chacinska, A. (2015). Retro-translocation of mitochondrial intermembrane space proteins. Proc Natl Acad Sci U S A. 112, 7713-7718.
  • Barchiesi, A., Wasilewski, M., Chacinska, A., Tell, G., Vascotto, C. (2015). Mitochondrial translocation of APE1 relies on the MIA pathway. Nucleic Acids Res. 43, 5451-5464.
  • Chojnacka, M., Gornicka, A., Oeljeklaus, S., Warscheid, B., Chacinska, A. (2015). Cox17 Protein Is an Auxiliary Factor Involved in the Control of the Mitochondrial Contact Site and Cristae Organizing System. J Biol Chem. 290, 15304-15312.
  • Ieva, R., Schrempp, S.G., Opaliński, L., Wollweber, F., Höß, P., Heißwolf, A.K., Gebert, M., Zhang, Y., Guiard, B., Rospert, S., Becker, T., Chacinska, A., Pfanner, N., van der Laan, M. (2014). Mgr2 functions as lateral gatekeeper for preprotein sorting in the mitochondrial inner membrane. Mol Cell 56, 641-652.
  • Gornicka, A., Bragoszewski, P., Chroscicki, P., Wenz, L.S., Schulz, C., Rehling, P., Chacinska, A. (2014). A discrete pathway for the transfer of intermembrane space proteins across the outer membrane of mitochondria . Mol Biol Cell 25, 3999-4009.
  • Melin, J., Schulz, C., Wrobel, L., Bernhard, O., Chacinska, A., Jahn, O., Schmidt, B., Rehling, P. (2014). Presequence recognition by the tom40 channel contributes to precursor translocation into the mitochondrial matrix. Mol Cell Biol 34, 3473-3485.
  • Sokol, A.M., Sztolsztener, M.E., Wasilewski, M., Heinz, E., Chacinska, A. (2014). Mitochondrial protein translocases for survival and wellbeing. FEBS Lett. 588, 2484-2485.
  • Pfanner, N., van der Laan, M., Amati, P., Capaldi, R.A., Caudy, A.A., Chacinska, A., Darshi, M., Deckers, M., Hoppins, S., Icho, T., Jakobs, S., Ji, J., Kozjak-Pavlovic, V., Meisinger, C., Odgren, P.R., Park, S.K., Rehling, P., Reichert, A.S., Sheikh, M.S., Taylor, S.S., Tsuchida, N., van der Bliek, A.M., van der Klei, I.J., Weissman, J.S., Westermann, B., Zha, J., Neupert, W., Nunnari, J. (2014). Uniform nomenclature for the mitochondrial contact site and cristae organizing system. J Cell Biol 204, 1083-1086.
  • Qiu, J., Wenz, L.S., Zerbes, R.M., Oeljeklaus, S., Bohnert, M., Stroud, D.A., Wirth, C., Ellenrieder, L., Thornton, N., Kutik, S., Wiese, S,, Schulze-Specking, A., Zufall, N., Chacinska, A., Guiard, B., Hunte, C., Warscheid, B., van der Laan, M., Pfanner, N., Wiedemann, N., and Becker, T. (2013). Coupling of mitochondrial import and export translocases by receptor-mediated supercomplex formation. Cell 154, 596-608.
  • Varabyova, A., Topf, U., Kwiatkowska, P., Wrobel, L., Kaus-Drobek, A., and Chacinska, A. (2013). Mia40 and MINOS act in parallel with Ccs1 in the biogenesis of mitochondrial Sod1. FEBS J 280, 4943-4959.
  • Bragoszewski, P., Gornicka, A., Sztolsztener, M.E., and Chacinska, A. (2013). The ubiquitin-proteasome system regulates mitochondrial intermembrane space proteins. Mol Cell Biol 33, 2136-48.
  • Wrobel, L., Trojanowska, A., Sztolsztener, M.E., and Chacinska, A. (2013). Mitochondrial protein import: Mia40 facilitates Tim22 translocation into the inner membrane of mitochondria.  Mol Biol Cell 24, 543-554.
  • Varabyova, A., Stojanovski, D., and Chacinska, A. (2013). Mitochondrial protein homeostasis. IUBMB Life 65, 191-201.
  • Sztolsztener, M.E., Brewinska, A., Guiard, B., and Chacinska, A. (2013). Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40. Traffic 14, 309-320.
  • Böttinger, L., Gornicka, A., Czerwik, T., Bragoszewski, P., Loniewska-Lwowska, A., Schulze-Specking, A., Truscott, K.N., Guiard, B., Milenkovic, D., and Chacinska, A. (2012). In vivo evidence for cooperation of Mia40 and Erv1 in the oxidation of mitochondrial proteins. Mol Biol Cell 23, 3957-3969.
  • Bohnert, M., Wenz, L.S., Zerbes, R.M., Horvath, S.E., Stroud, D.A., von der Malsburg, K., Muller, J.M., Oeljeklaus, S., Perschil, I., Warscheid, B., Chacinska, A., Veenhuis, M., van der Klei, I.J., Daum, G., Wiedemann, N., Becker, T., Pfanner, N., van der Laan, M. (2012). Role of mitochondrial inner membrane organizing system in protein biogenesis of the mitochondrial outer membrane. Mol Biol Cell 23, 3948-3956.
  • Stojanovski, D., Bragoszewski, P., and Chacinska, A. (2012). The MIA pathway: A tight bond between protein transport and oxidative folding in mitochondria. Biochim Biophys Acta 1823, 1142-1150.
  • von der Malsburg, K., Müller, J.M., Bohnert, M., Oeljeklaus, S., Kwiatkowska, P., Becker, T., Loniewska-Lwowska, A., Wiese, S., Rao, S., Milenkovic, D., Hutu, D.P., Zerbes, R.M., Schulze-Specking, A., Meyer, H.E., Martinou, J.C., Rospert, S., Rehling, P., Meisinger, C., Veenhuis, M., Warscheid, B., van der Klei, I.J., Pfanner ,N.*, Chacinska, A.*, van der Laan, M. (2011). Dual Role of Mitofilin in Mitochondrial Membrane Organization and Protein Biogenesis. Developmental Cell, 21, 694-707. (*co-corresponding author)
  • Becker, T., Wenz, L.S., Krüger, V., Lehmann, W., Müller, J.M., Goroncy, L., Zufall, N., Lithgow, T., Guiard, B., Chacinska, A., Wagner, R., Meisinger, C., Pfanner, N. (2011). The mitochondrial import protein Mim1 promotes biogenesis of multispanning outer membrane proteins. J Cell Biol 194, 387-95.
  • Schulz, C., Lytovchenko, O., Melin, J., Chacinska, A., Guiard, B., Neumann, P., Ficner, R., Jahn, O., Schmidt, B., Rehling, P. (2011). Tim50’s presequence receptor domain is essential for signal driven transport across the TIM23 complex. J Cell Biol 195, 643-56.
  • Chacinska, A., van der Laan, M., Mehnert, C.S., Guiard, B., Mick, D.U., Hutu, D.P., Truscott, K.N., Wiedemann, N., Meisinger, C., Pfanner, N., Rehling, P. (2010). Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting. Mol Cell Biol 30, 307-318.
  • Voegtle, F. N., Schmidt, O., Chacinska, A., Pfanner, N., Meisinger, C. (2010). Native techniques for analysis of mitochondrial protein import. Methods Mol Biol 619, 425-436.
  • Chacinska, A., Koehler, C.M., Milenkovic, D., Lithgow, T., Pfanner, N. (2009). Importing mitochondrial proteins: machineries and mechanisms. Cell 138, 628-644.
  • 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.
  • Baker, M.J., Webb, C.T., Stroud, D.A., Palmer, C.S., Frazier, A.E., Guiard, B., Chacinska, A., Gulbis, J.M., Ryan M. (2009). Structural and functional requirements for activity of the Tim9-Tim10 complex in mitochondrial protein import. Mol Biol Cell 20, 769-779.
  • 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. (*co-corresponding author)
  • 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).
  • 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.
  • Hutu, D.P., Guiard, B., Chacinska, A., Becker, D., Pfanner, N., Rehling, P., van der Laan, M. (2008). Mitochondrial protein import motor: differential role of Tim44 in the recruitment of Pam17 and J-complex to the presequence translocase. Mol Biol Cell 19, 2642-2649.
  • Gebert, N., Chacinska, A., Wagner, K., Guiard, B., Koehler, C.M., Rehling, P., Pfanner, N., Wiedemann, N. (2008). Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase. EMBO Rep 9, 548-554.
  • Stojanovski, D., Müller, J.M., Milenkovic, D., Guiard, B., Pfanner, N., Chacinska, A. (2008). The MIA system for protein import into the mitochondrial intermembrane space. Biochim Biophys Acta 1783, 610-617.
  • 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.
  • Milenkovic, D., Müller, J.M.M., Stojanovski, D., Pfanner, N., Chacinska, A. (2007). Diverse mechanisms and machineries for import of mitochondrial proteins.  Biol Chem 388, 891-897.
  • Meisinger, C., Pfannschmidt, S., Rissler, M., Milenkovic, D., Becker, t., Stojanovski, D., Youngman, M.J., Jensen, R.E., Chacinska, A., Guiard, B., Pfanner, N., Wiedemann, N. (2007). The morphology proteins Mdm12/Mmm1 function in the major beta-barrel assembly pathway of mitochondria. EMBO J 26, 2229-2239.
  • Sanjuán Szklarz, L.K., Kozjak-Pavlovic, V., Vogtle, F.N., Chacinska, A., Milenkovic, D., Vogel, S., Durr, M., Westermann, B., Guiard, B., Martinou, J.C., Borner, C., Pfanner, N., and Meisinger, C. (2007). Preprotein transport machineries of yeast mitochondrial outer membrane are not required for Bax-induced release of intermembrane space proteins. J Mol Biol 368, 44-54.
  • Gabriel, K., Milenkovic, D., Chacinska, A., Muller, J., Guiard, b., Pfanner, N., and Meisinger, C. (2007). Novel mitochondrial intermembrane space proteins as substrates of the MIA import pathway. J Mol Biol 365, 612-620.
  • Wiedemann, N., Pfanner, N., and Chacinska, A. (2006). Chaperoning through the mitochondrial intermembrane space. Mol Cell 21, 145-148.
  • Meinecke, M., Wagner, R., Kovermann, P., Guiard, B., Mick, D.U., Hutu, D.P., Voos, W., Truscott, K.N., Chacinska, A., Pfanner, N., and Rehling, P. (2006). Tim50 maintains the permeability barrier of the mitochondrial inner membrane. Science 312, 1523-1526.
  • Albrecht, R., Rehling, P., Chacinska, A., Brix, J., Cadamuro, S.A., Volkmer, R., Guiard, B., Pfanner, N., Zeth, K. (2006). Tim21 binding domain connects the preprotein translocase of both mitochondrial membranes. EMBO Rep 7, 1233-1238.
  • Rospert, S., and Chacinska, A. (2006). Distinct yet linked: chaperone networks in the eukaryotic cytosol. Genome Biol 7, 208.
  • 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.
  • van der Laan, M.*, Chacinska, A.*, Lind, M., Perschil, I., Sickmann, A., Meyer, H.E., Guiard, B., Meisinger, C., Pfanner, N., and Rehling, P. (2005). Pam17 is required for architecture and translocation activity of the mitochondrial protein import motor. Mol Cell Biol 25, 7449-7458 (*equal contribution).
  • Sanjuán Szklarz, L.K., Guiard, B., Rissler, M., Wiedemann, N., Kozjak, V., van der Laan, M., Lohaus, C., Marcus, K., Meyer, H.E., Chacinska, A., Pfanner, N., and Meisinger, C. (2005). Inactivation of the mitochondrial heat shock protein Zim17 leads to aggregation of matrix Hsp70s followed by pleiotropic effects on morphology and protein biogenesis. J Mol Biol 351, 206-218.
  • 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., and Rehling, P. (2004). Moving proteins from the cytosol into mitochondria. Biochem Soc Trans 32, 774-776.
  • Meisinger, C., Rissler, M., Chacinska, A., Sanjuán Szklarz, L.K., Milenkovic, D., Kozjak, V., Schönfisch, B., Lohaus, C., Meyer, H.E., Yaffe, M.P., Guiard, B., Wiedemann, N., and Pfanner, N. (2004). The mitochondrial morphology protein Mdm10 functions in assembly of the preprotein translocase of the outer membrane. Developmental Cell 7, 61-71.
  • Towpik, J., Chacinska, A., Ciesla, M., Ginalski, K., and Boguta, M. (2004). Mutations in yeast MRF1 gene encoding mitochondrial release factor inhibit translation on mitochondrial ribosomes. J Biol Chem 279, 14096-14103.
  • Chacinska, A., Rehling, P., Guiard, B., Frazier, A.E., Schulze-Specking, A., Pfanner, N., Voos, W., and Meisinger, C. (2003). Mitochondrial translocation contact sites: separation of dynamic and stabilizing elements in formation of a TOM-TIM-preprotein supercomplex. EMBO J 22, 5370-5381.
  • Frazier, A.E., Chacinska, A., Truscott, K.N., Guiard, B., Pfanner, N., and Rehling, P. (2003). Mitochondria use different mechanisms for transport of multispanning membrane proteins through the intermembrane space. Mol Cell Biol 23, 7818-7828.
  • Sickmann, A., Reinders, J., Wagner, Y., Joppich, C. Zahedi, R., Meyer, H.E., Schönfisch, B., Perschil, I., Chacinska, A., Guiard, B., Rehling, P., Pfanner, N., and Meisinger, C. (2003). The proteome of Saccharomyces cerevisiae mitochondria. Proc Natl Acad Sci USA 100, 13207-13212.
  • Wiedemann, N., Kozjak, V., Chacinska, A., Schönfisch, B., Rospert, S., Ryan, M.T., Pfanner, N., and Meisinger, C. (2003). Machinery for protein sorting and assembly in the mitochondrial outer membrane. Nature 424, 565-571.
  • Geissler, A.*, Chacinska, A.*, Truscott, K.N., Wiedemann, N., Brandner, K., Sickmann, A., Meyer, H.E., Meisinger, C., Pfanner, N., and Rehling, P. (2002). The mitochondrial presequence translocase: an essential role of Tim50 in directing preproteins to the import channel. Cell 111, 507-518 (*equal contribution).
  • Chacinska, A., Pfanner, N., and Meisinger, C. (2002). How mitochondria import hydrophilic and hydrophobic proteins. Trends Cell Biol 12, 299-303.
  • Pfanner, N. and Chacinska, A. (2002). The mitochondrial import machinery: preprotein-conducting channels with binding sites for presequences. Biochim Biophys Acta 1592, 15-24.
  • Chacinska, A., Szczesniak, B., Kochneva-Pervukhova, N. V., Kushnirov, V.V., Ter-Avanesyan, M.D., and Boguta, M. (2001). Ssb1 chaperone is a [PSI+] prion-curing factor. Curr Genet 39, 62-67.
  • Chacinska, A., Boguta, M., Krzewska, J. and Rospert, S. (2000). Prion-dependent switching between respiratory competence and deficiency in the yeast nam9-1 mutant. Mol Cell Biol 20, 7220-9.
  • Chacinska, A., Boguta, M. (2000). Coupling of mitochondrial translation with the formation of respiratory complexes in yeast mitochondria. Acta Biochim Pol 47, 973-91.
  • Boguta, M., Chacinska, A., Murawski, M. and Szczesniak, B. (1997). Expression of the yeast NAM9 gene coding for mitochondrial ribosomal protein. Acta Biochim Pol 44, 251-8.
  • Gora, M., Chacinska, A., Rytka, J. and Labbe-Bois, R. (1996). Isolation and functional characterization of mutant ferrochelatases in Saccharomyces cerevisiae. Biochimie 78, 144-52.

 


Title Project Leader Project period Project funding
Cross-talk between the transport of mitochondrial proteins and cellular protein homeostasis Agnieszka Chacińska 2016 - 2021 MAESTRO, NCN
Cellular mechanisms handling failed mitochondrial protein translocation events. Piotr Brągoszewski 2017 - 2020 FirstTeam, FNP
The interplay between the translation machinery and the mitochondrial dysfunction under cellular stress. Urszula Nowicka 2017 - 2019 HOMING, FNP
Analysis of the alternative import pathways of mitochondrial proteins. Aleksandra Gosk 2017 - 2019 Diamentowy Grant, MNiSW
Mitochondrial translocation of the DNA repair protein AP1. Carlo Vascotto 2017 - 2019 POLONEZ, NCN
Analysis of the mitochondrial proteins translocase TIM22 in human cells. Katarzyna Chojnacka 2016 - 2019 FUGA, NCN
Mechanisms protecting from oxidative damage during aging. Ulrike Topf 2016 - 2019 OPUS10, NCN
Characterization of the TIM23 pathway of protein import into mitochondria in mammalian cells. Michał Wasilewski 2016 - 2019 OPUS10, NCN
The link between mitochondria and the protein quality control system. Michał Turek 2017 - 2019 POLONEZ, NCN
Principles of mitochondrial protein compartmentalization in vertebrates Barbara Uszczyńska-Ratajczak 2017 - 2019 POLONEZ, NCN
Cytosolic chaperone systems for mitochondrial precursor proteins. Agnieszka Chacińska 2014 - 2018 Ideas Plus, MNiSW
Coupling of synthesis and transport for proteins targeted to the mitochondria. Agnieszka Chacińska 2014 - 2018 OPUS, NCN
Extramitochondrial factors regulating turnover of mitochondrial intermembrane space proteins. Piotr Brągoszewski 2014 - 2017 SONATA6, NCN
Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species.
Topf, U., Suppanz, I., Samluk, L., Wrobel, L., Böser, A., Sakowska, P., Knapp, B., Pietrzyk, M.K., Chacinska, A. and Warscheid, B. (2018)
Nature Communications, 9(1), p.324.
Determinants of the cytosolic turnover of mitochondrial intermembrane space proteins.
Kowalski L, Bragoszewski P, Khmelinskii A, Glow E, Knop M, Chacinska A. (2018)
BMC Biol. 2018 Jun 22;16(1):66. doi: 10.1186/s12915-018-0536-1.
Mitochondrial protein import stress and signaling
Samluk, L., Chroscicki, P., & Chacinska, A. (2018).
Current Opinion in Physiology
Motor recruitment to the TIM23 channel’s lateral gate restricts polypeptide release into the inner membrane.
Schendzielorz, A. B., Bragoszewski, P., Naumenko, N., Gomkale, R., Schulz, C., Guiard, B., ... & Rehling, P. (2018)
Nature communications, 9(1), 4028
Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish.
Sokol, A. M., Uszczynska-Ratajczak, B., Collins, M. M., Bazala, M., Topf, U.,.... & Chacinska, A. (2018)
PLoS Genetics
Control of mitochondrial biogenesis and function by the ubiquitin–proteasome system.
Bragoszewski, P., Turek, M. and Chacinska, A. (2017)
Open biology 7, no. 4: 170007.
Cell biology: Sort and destroy.
Chacinska, A. (2017)
Nature 543, no. 7645: 324-325.
High-throughput annotation of full-length long noncoding RNAs with capture long-read sequencing.
Lagarde, J., Uszczynska-Ratajczak, B., Carbonell, S., Perez-Lluch, S., Abad, A., Davis, C., ... & Johnson, R. (2017)
Nature genetics, 49(12), 1731.
Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo-tomography.
Gold, V. A., Chroscicki, P., Bragoszewski, P., & Chacinska, A. (2017)
EMBO reports, 18(10), 1786-1800.
Title Deadline for applications
Bioinformatician / Computational Biologist 16/12/2018

Project number: 2015/18/A/NZ1/00025

Project title: Cross-talk between the transport of mitochondrial proteins and cellular protein homeostasis

Project leader:

Agnieszka Chacinska, PhD, Professor
E: a.chacinska@dev.dev.cent.uw.edu.pl/en

Post-doctoral researchers:

Michal Turek, PhD
E: m.turek@dev.dev.cent.uw.edu.pl/en

Anna Antosiewicz, PhD
E: a.antosiewicz@dev.dev.cent.uw.edu.pl/en

PhD students:

Maria Sladowska, Martyna Pietrzyk

Source of funding: National Science Centre, Poland

Budget: 4 271 581 PLN

Project duration: 21.04.2016 – 20.04.2021

About the project:

Mitochondrion is a cellular compartment commonly known as “the power plant” of cells. To fulfill its various functions, this organelle needs more than one thousand cellular proteins. Yet, the majority of mitochondrial proteins are synthesized outside mitochondria in the cytosol and thus must be transported into mitochondria with the help of other proteins forming import machines. Dysfunctional mitochondrial protein import machines cause mitochondrial malfunctions, but also accumulation of precursor proteins in the cytosol. The Chacinska group discovered the role of the cytosolic degradation machinery in precursors’ clearance and the mechanism called the unfolded protein response activated by mistargeted proteins (UPRam) that protects the cell from stress caused by mistargeted mitochondrial precursor proteins accumulating in the cytosol. These processes pinpoint an important crosstalk between the state of mitochondria and regulatory mechanisms responsible for maintaining the cellular protein homeostasis. In the Maestro project, using simple model organisms, such as yeasts and worms, in addition to cultured mammalian cells, multidisciplinary approaches based on biochemistry, molecular cell biology and systems biology will be undertaken to identify and characterize the mechanisms of both, degradation of mistargeted mitochondrial proteins and the UPRam. We also aim to uncover biological consequences of these mechanisms, which are critical for homeostasis, survival and ageing at the cellular and organismal level.

Publications:

Wasilewski M., Chojnacka K., Chacinska A. Protein trafficking at the crossroads to mitochondria. 2017. Biochim Biophys Acta, 1864(1):125-137.

Lectures at the international conferences:

11.2016

Chacinska A. – Invited Speaker, International Conference of the Centre for Misfolding
Diseases 2016, “Protein homeostasis at the crossroads to mitochondria”,
Sevilla, Spain

11.2016

Chacinska A. – Invited Speaker, Protein Biogenesis & Mitochondrial Dynamics, “Protein
trafficking at the crossroads to mitochondria”, Baiersbronn-Obertal, Germany

09.2016

Turek M., The 2nd Congress BIO 2016: “Expanding beyond the limits”, Wroclaw, Poland

Posters at the international conferences:

09.2016

Sladowska M., Topf U., Chacinska A., Poster Session at the 7th EMBO meeting, “Effects of mitochondrial dysfunction in Caenorhabditis elegans”, Mannheim, Germany

The „Regenerative Mechanisms for Health” International Research Agenda Unit (“ReMedy”) is a joint unit of the University of Warsaw and University Medical Center Göttingen at Georg-August-University Göttingen, funded by a grant by the Foundation for Polish Science. The goal of ReMedy is to understand and to harness stress‐evoked adaptability of cells at the molecular and biochemical level, in order to combat human diseases and pathologies.
Director: Prof. Agnieszka Chacińska (a.chacinska@dev.dev.cent.uw.edu.pl/en)
Deputy director: Prof. Magda Konarska (m.konarska@dev.dev.cent.uw.edu.pl/en)
Project coordinator: Michał Wrzesiński, PhD (m.wrzesinski@dev.dev.cent.uw.edu.pl/en)
ReMedy aims to:

  • understand mechanisms of stress response
  • discover short- and long‐term consequences of cellular responses and their crosstalk in physiology
  • apply the gained knowledge about stress responses for the development of new medical treatments.
Prof. Chacińska will seek to identify global consequences of translational inhibition in human cells. Preliminary data show that although acute stress leads to rapid inhibition of protein synthesis, this stress is not lethal and frequently cells become even more resistant to further insults. Unknown adaptive mechanisms lead to re-initiation of protein translation. Prof. Chacińska’s group will undertake a system analysis of gene expression changes that accompany dysfunctional mitochondria, aiming to identify changes in transcription various steps of mRNA biogenesis and stability, including splicing – in collaboration with the Konarska lab – as well as translation activity/recruitment of mRNA during translation initiation. Studies of the group will deliver a comprehensive gene expression profiling under mitochondrial dysfunction and will lead to a discovery of yet unknown responses and adaptive pathways that have a potential to rescue cells and organisms from organellar stress and may in general benefit cellular and organismal fitness.

Prof. Konarska group will study the mechanisms by which aging or environmental signals influence the function of the splicing machinery and affect splicing outcomes. Changes in patterns of alternative splicing in higher eukaryotes are characteristic signatures of stress and disease, but little is known about the underlying mechanisms. These studies will help to understand how environmental changes or ageing affect regulation of gene expression at the splicing level. They will also help to understand the function of the spliceosome and suggest new ways to modulate it. Ultimately, the mechanisms utilized by yeast to regulate pre-mRNA splicing will also be validated in mammalian cells, and the way how they affect more complex regulation of alternative splicing will be studied in collaboration with the Chacińska group.

 

ReMedy is funded by Foundation for Polish Science International Research Agendas Programme (project MAB/2017/2) under measure 4.3 “International Research Agendas“, Smart Growth Operational Programme 2014-2020.
Call for group leaders
The call for the first two new Group Leaders, of the final group of five, is now open. We highly encourage you to see the offer at the following link.