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  • Laboratory of Mitochondrial Biogenesis: Chacinska Laboratory

Laboratory of Mitochondrial Biogenesis: Chacinska Laboratory

Description of Current Research

   Mitochondria play an important role in metabolism and regulatory processes in the cell. Thus, the formation of mitochondria is essential for cellular function in the entire 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 governed by conserved protein translocases and other complex machineries. We identified a novel mitochondrial intermembrane space assembly (MIA) pathway that 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:
•    Redox-related biogenesis events of mitochondrial proteins in yeast and higher eukaryotes.
•    The impact of the MIA pathway on mitochondrial and cellular protein homeostasis.
•    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, the maintenance of mitochondrial protein homeostasis, and their failure, which results in pathology.

 

We are always interested in qualified and highly motivated students and postdocs.  Please inquire: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Our recent publication:

Wrobel L, Topf U, Bragoszewski P , Wiese S, Sztolsztener ME , Oeljeklaus S, Varabyova A, Lirski M, Chroscicki P, Mroczek S, Januszewicz E, Dziembowski A, Koblowska M, Warscheid B, Chacinska A. Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. 2015. Nature, 524(7566), 485-8.
 

UPRam_scheme

Agnieszka Chacińska, PhD, Professor

Education and Degrees:
2014  Professor of Biological Sciences, nomination by the President of the Republic of Poland
2008  DSc Habil, Institute of Biochemistry and Biophysics, Warsaw, Poland
2000  PhD in Biochemistry, Institute of Biochemistry and Biophysics, Warsaw
1993  Master Degree in Molecular Biology, University of Warsaw
1988-1993  Biology, University of Warsaw, Poland


Awards:
2016 Award from the Premiere for the 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
2010  EMBO Installation Grant
2009  Welcome Programme, Foundation for Polish Science
2008  Eugen-Graetz Prize for Research, University of Freiburg, Germany
2001-2003  Long-term FEBS fellowship
2001  Award for PhD thesis, Institute of Biochemistry and Biophysics, Warsaw
1997  Grant for young scientists, Polish State Committee for Scientific Research
1996  Short-term FEBS fellowship


Research experience and appointments:
2015 – present Deputy Director of Development at the International Institute of Molecular and Cell Biology in Warsaw, Poland
2009 - present  Professor and Leader of Laboratory of Mitochondrial Biogenesis, International Institute of Molecular and Cell Biology, Warsaw, Poland
2008-2009  Associate Member of Excellence Cluster BIOSS, Centre for Biological Signalling Studies, University of Freiburg, Germany
2007-2009  Member of the Board, Collaborative Research Centre (SFB 746)
2007-2010  Project Leader in Collaborative Research Centre (SFB 746), Germany
2004-2009  Group Leader (German equivalent of Assistant Professor), Institute for  Biochemistry and Molecular Biology, University of Freiburg, Germany
2001-2004  Postdoctoral Fellow, Laboratory of Prof. Nikolaus Pfanner, University of Freiburg, Germany
1999  Visiting Scientist, Laboratory of Prof. Sabine Rospert, Max Planck Research Unit, Halle, Germany
1997  Visiting Scientist, 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

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

 

For recent publications see Research Focus and Publications

  
Pubmed search for Chacinska A

 

Selected publications from my group in Freiburg:

 

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.

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.

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.

Stojanovski, D., Müller, JM, 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.

Wiedemann, N., Pfanner, N., and Chacinska, A. (2006). Chaperoning through the mitochondrial intermembrane space. Mol. Cell 21, 145-148.

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.

Selected publications arising from my post-doctoral research:

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).

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).

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., 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.

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).

Other important contributions:

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.

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. Dev. Cell 7, 61-71.

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.

The most important paper from my PhD studies:

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.
images/labs/chacinska/banner_2014_2e_v2-01.png
 
 
Lab Leader:Laboratory of Mitochondrial Biogenesis
Agnieszka Chacińska, PhD, Professor
This email address is being protected from spambots. You need JavaScript enabled to view it.
+48 22 59 70 779
 
Lab and Office Manager:
Maria Łepkowska, BSc
This email address is being protected from spambots. You need JavaScript enabled to view it.
+48 22 59 70 605

Postdoctoral Fellows:
Piotr Brągoszewski, PhD
Katarzyna Chojnacka, PhD
Łukasz Samluk, PhD
Anna Sokół, PhD
Ulrike Topf, PhD
Michał Wasilewski, PhD
Michal Turek, PhD
Paulina Sakowska, PhD

PhD Students:
Magdalena Chojnacka, MSci
Piotr Chrościcki, MSc
Łukasz Kowalski, MSc
Karthik Mohanraj, MSc
Maria Śladowska, MSci
Anna Antosiewicz, MSc
Martyna Pietrzyk, Msci

FishMed Research Assistant:
Michał Bazała, MSc

Research Technician:
Elżbieta Grzelak

Sabbatical Professor:
Dr. Carlo Vascotto

Former students and co-workers of Laboratory of Mitochondrial Biogenesis:
Arianna Barchiesi, MSc
Anita Brewińska, MSc
Tomasz Czerwik, MSc
Magdalena Długołęcka, MSci
Beata Drabarek, PhD
Aleksandra Fergin, MSc
Edyta Głów, MSc
Agnieszka Górnicka, PhD
Elżbieta Januszewicz, PhD
Magdalena Kaus-Drobek, PhD
Adrianna Łoniewska-Lwowska, PhD
Aleksandra Matusiak, MSci
Inmaculada Mora Espi, MSc
Kamila Ornoch, MSc
Małgorzata Sztolsztener, PhD
Krzysztof Tarasiuk, MSci
Agata Trojanowska, MSc
Aksana Varabyova, PhD
Jakub Dominowski, MSci
Lidia Wróbel, PhD
Sabine Poerschke

 

 

2018

Topf U, Suppanz I, Samluk L, Wrobel L, Böser A, Sakowska P, Knapp B, Pietrzyk MK, Chacinska A, Warscheid B.

Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species.

Kowalski L, Bragoszewski P, Khmelinskii A, Glow E, Knop M, Chacinska A.

Determinants of the cytosolic turnover of mitochondrial intermembrane space proteins.

Sokol AM, Uszczynska-Ratajczak B, Collins MM, Bazala M, Topf U, Lundegaard PR, Sugunan S, Guenther S, Kuenne C, Graumann J, Chan SSL, Stainier DYR, Chacinska A.

Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish.

2017

Bragoszewski P, Turek M, Chacinska A.

Control of mitochondrial biogenesis and function by the ubiquitin-proteasome system

Chacinska A.

Cell biology: Sort and destroy

Gold VA, Chroscicki P, Bragoszewski P, Chacinska A.

Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo-tomography.

2016

Topf U, Wrobel L, Chacinska A

Chatty Mitochondria: Keeping Balance in Cellular Protein Homeostasis

Wrobel L, Sokol AM, Chojnacka M, Chacinska A

The presence of disulfide bonds reveals an evolutionarily conserved mechanism involved in mitochondrial protein translocase assembly

Turakhiya U, von der Malsburg K, Gold VA, Guiard B, Chacinska A, van der Laan M, Ieva R

Protein Import by the Mitochondrial Presequence Translocase in the Absence of a Membrane Potential

Callegari S, Richter F, Chojnacka K, Jans DC, Lorenzi I, Pacheu-Grau D, Jakobs S, Lenz C, Urlaub H, Dudek J, Chacinska A, Rehling P

TIM29 is a subunit of the human carrier translocase required for protein transport

Wasilewski M, Chojnacka K, Chacinska A

Białka mitochondrialne – import, eksport, degradacja

Wasilewski M, Chojnacka K, Chacinska A

Protein trafficking at the crossroads to mitochondria

2015

Barchiesi A, Wasilewski M, Chacinska A, Tell G, Vascotto C

Mitochondrial translocation of APE1 relies on the MIA pathway

Chojnacka M, Gornicka A, Oeljeklaus S, Warscheid B, Chacinska A

Cox17 is an auxiliary factor involved in the control of the mitochondrial contact site and cristae organizing system

Bragoszewski P, Wasilewski M, Sakowska P, Gornicka A, Böttinger L, Qiu J, Wiedemann N, Chacinska A

Retro-translocation of mitochondrial intermembrane space proteins

Wrobel L, Topf U, Bragoszewski P , Wiese S, Sztolsztener ME , Oeljeklaus S, Varabyova A, Lirski M, Chroscicki P, Mroczek S, Januszewicz E, Dziembowski A, Koblowska M, Warscheid B, Chacinska A

Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol

Sakowska P, Jans DC, Mohanraj K, Riedel D, Jakobs S, Chacinska A

The oxidation status of Mic19 regulates MICOS assembly

Keatinge M, Bui H, Menke A, Chen YC, Sokol AM, Bai Q, Ellett F, Da Costa M, Burke D, Gegg M, Trollope L, Payne T, McTighe A, Mortiboys H, de Jager S, Nuthall H, Kuo MS, Fleming A, Schapira AH, Renshaw SA, Highley JR, Chacinska A, Panula P, Burton EA, O'Neill MJ, Bandmann O

Glucocerebrosidase 1 deficient Danio rerio mirror key pathological aspects of human Gaucher disease and provide evidence of early microglial activation preceding alpha-synuclein-independent neuronal cell death

2014

Ieva R, Schrempp SG, Opaliński L Wollweber F, Höß P, Heißwolf AK, Gebert M, Zhang Y, Guiard B, Rospert S, Becker T, Chacinska A, Pfanner N, van der Laan M

Mgr2 functions as lateral gatekeeper for preprotein sorting in the mitochondrial inner membrane

Pfanner N, van der Laan M, Amati P, Capaldi RA, Caudy AA, Chacinska A, Darshi M, Deckers M, Hoppins S, Icho T, Jakobs S, Ji J, Kozjak-Pavlovic V, Meisinger C, Odgren PR, Park SK, Rehling P, Reichert AS, Sheikh MS, Taylor SS, Tsuchida N, van der Bliek AM, van der Klei IJ, Weissman JS, Westermann B, Zha J, Neupert W, Nunnari J

Uniform nomenclature for the mitochondrial contact site and cristae organizing system

Sokol AM, Sztolsztener ME, Wasilewski M, Heinz E, Chacinska A

Mitochondrial protein translocases for survival and wellbeing

Melin J, Schulz C, Wrobel L, Bernhard O, Chacinska A, Jahn O, Schmidt B, Rehling P

Presequence recognition by the tom40 channel contributes to precursor translocation into the mitochondrial matrix

Gornicka A, Bragoszewski P, Chroscicki P, Wenz LS, Schulz C, Rehling P, Chacinska A

A discrete pathway for the transfer of intermembrane space proteins across the outer membrane of mitochondria

2013

Sztolsztener ME, Brewinska A, Guiard B, Chacinska A

Disulfide bond formation: sulfhydryl oxidase ALR controls mitochondrial biogenesis of human MIA40

Varabyova A, Stojanovski D, Chacinska A

Mitochondrial protein homeostasis

Wrobel L, Trojanowska A, Sztolsztener ME, Chacinska A

Mitochondrial protein import: Mia40 facilitates Tim22 translocation into the inner membrane of mitochondria

Bragoszewski P, Gornicka A, Sztolsztener ME, Chacinska A

The ubiquitin-proteasome system regulates mitochondrial intermembrane space proteins

Varabyova A, Topf U, Kwiatkowska P, Wrobel L, Kaus-Drobek M, Chacinska A

Mia40 and MINOS act in parallel with Ccs1 in the biogenesis of mitochondrial Sod1

Qiu J, Wenz LS, Zerbes RM, Oeljeklaus S, Bohnert M, Stroud DA, 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, Becker T

Coupling of mitochondrial import and export translocases by receptor-mediated supercomplex formation

2012

Stojanovski D, Bragoszewski P, Chacinska A

The MIA pathway: A tight bond between protein transport and oxidative folding in mitochondria

Bohnert M, Wenz LS, Zerbes RM, Horvath SE, Stroud DA, von der Malsburg K, Müller JM, Oeljeklaus S, Perschil I, Warscheid B, Chacinska A, Veenhuis M, van der Klei IJ, Daum G, Wiedemann N, Becker T, Pfanner N, van der Laan M

Role of MINOS in protein biogenesis of the mitochondrial outer membrane

Voegtle FN, Burkhart JM, Rao S, Gerbeth C, Hinrichs J, Martinou JC, Chacinska A, Sickmann A, Zahedi RP, Meisinger C

Intermembrane space proteome of yeast mitochondria

Böttinger L*, Gornicka A*, Czerwik T, Bragoszewski P, Loniewska-Lwowska A, Schulze-Specking A, Truscott KN, Guiard B, Milenkovic D, Chacinska A, *equally contributing first author

In vivo evidence for cooperation of Mia40 and Erv1 in the oxidation of mitochondrial proteins

2011

Becker T, Wenz LS, Krüger V, Lehmann W, Müller JM, Goroncy L, Zufall N, Lithgow T, Guiard B, Chacinska A, Wagner R, Meisinger C, Pfanner N

The mitochondrial import protein Mim1 promotes biogenesis of multispanning outer membrane proteins

von der Malsburg K, Müller JM, Bohnert M, Oeljeklaus S, Kwiatkowska P, Becker T, Loniewska-Lwowska A, Wiese S, Rao S, Milenkovic D, Hutu DP, Zerbes RM, Schulze-Specking A, Meyer HE, Martinou JC, Rospert S, Rehling P, Meisinger C, Veenhuis M et all

Dual role of mitofilin in mitochondrial membrane organization and protein biogenesis

Schulz C, Lytovchenko O, Melin J, Chacinska A, Guiard B, Neumann P, Ficner R, Jahn O, Schmidt B, Rehling P

Tim50's presequence receptor domain is essential for signal driven transport across the TIM23 complex

Milczarski P, Bolibok-Brągoszewska H, Myśków B, Stojałowski S, Heller-Uszyńska K, Góralska M, Brągoszewski P, Uszyński G, Kilian A, Rakoczy-Trojanowska M

A high density consensus map of rye (Secale cereale L.) based on DArT markers