Research group of Nikolaus Pfanner

Research

Biogenesis and Architecture of Mitochondria

Mitochondria are essential for the viability of eukaryotic cells. They play central functions in cellular ATP synthesis, the metabolism of amino acids and lipids, the biosynthesis of heme and Fe/S clusters, as well as in programmed cell death (apoptosis). Mitochondria consist of four subcompartments: outer membrane, intermembrane space, inner membrane and matrix. The inner membrane possesses a characteristic architecture with tubular invaginations (cristae) that increase the membrane surface several-fold. Defects of mitochondrial function and homeostasis lead to severe human diseases, in particular of the nervous system, heart and muscles.

Our studies focus on the following topics:

• Targeting of precursor proteins from the cytosol into mitochondria: molecular mechanisms and regulation of mitochondrial preprotein translocases
• Cooperation of translocases during transport and assembly of mitochondrial proteins: dynamic supercomplexes and protein networks
• Molecular architecture of the mitochondrial membranes: machineries forming membrane contact sites and maintaining the characteristic shape of mitochondria

Team

Funding

CV Nikolaus Pfanner

Since 1992	Professor and Chair of the Institute of Biochemistry and Molecular Biology, University of Freiburg
2008 ‑ 2017	Member of the Council of the University of Freiburg
2009 ‑ 2011	President of the German Society for Biochemistry and Molecular Biology (GBM)
2002 ‑ 2008	Chair of Research Board of Medical Faculty Freiburg
1995 ‑ 2006	Coordinator of Collaborative Research Center on “Cellular Functions of Dynamic Protein Interactions” (SFB 388)
1996 ‑ 2000	Chair of Study Section of  Biological Chemistry & Biophysics of the German Research Foundation (DFG)
1987 ‑ 1992	Research Group Leader, Institute of Physiological Chemistry, University of Munich
1988 ‑ 1989	Research Fellow, Department of Molecular Biology, Princeton University (Prof James Rothman)
1985 ‑ 1986	Postdoc, Physiological Chemistry, University of Munich (Prof. Walter Neupert)
1984 ‑ 1985	Dissertation, Institute of Physiological Chemistry, University of Munich (Prof. Walter Neupert)
1978 ‑ 1984	Medical studies, University of Munich
1956	Born in Simmerberg, Germany

Honors

Since 2020	Distinguished Guest Professor, Kyoto Sangyo University, Japan
2025	Walter Neupert Medal
2022/2023	Teacher of the Year Award, Faculty of Medicine Freiburg (for the 5th time since 1999 Best Lecturer, Faculty of Medicine / Preclinical / Molecular Medicine)
2021	Schleiden Medal of the German Academy of Sciences Leopoldina
2019	Honorary doctorate, Faculty of Medicine, University of Bochum
2018	Reinhart Koselleck Grant of the German Research Foundation (DFG)
2015	Otto Warburg Medal
2015	Order of Merit of the Federal Republic of Germany
2014	Stein and Moore Award of the Protein Society, USA
2014	Wilhelm-Feldberg-Prize, UK
2011	Hector Science Award
2008	Research Prize of the State of Baden-Württemberg
2007	Research Prize of the German Academy of Sciences Leopoldinav
2004	Gottfried Wilhelm Leibniz Prize
2002	Max Planck Research Award
1991	Research Prize of the University of Munich
1985	Summa cum laude, University of Munich

Elected Member

Since 2025	Accademia Nazionale dei Lincei, Italy (foreign member)
Since 2005	Academia Europaea
Since 2004	Academy of Sciences Heidelberg
Since 2000	German Academy of Sciences Leopoldina
Since 1994	European Molecular Biology Organisation (EMBO)

Publications

List of publications    

https://pubmed.ncbi.nlm.nih.gov/?term=Pfanner+N&sort=date

Selected publications 2025 – 2010    

• Pfanner N, den Brave F, Becker T: Mitochondrial protein import stress. Nat Cell Biol, 2025; 27: 188-201.
• Horten P, Song K, Garlich J, Hardt R, Colina-Tenorio L, Horvath SE, Schulte U, Fakler B, van der Laan M, Becker T, Stuart RA, Pfanner N, Rampelt H: Identification of MIMAS, a multifunctional mega-assembly integrating metabolic and respiratory biogenesis factors of mitochondria. Cell Rep, 2024; 43: 113772.
• Schulte U, den Brave F, Haupt A, Gupta A, Song J, Müller CS, Engelke J, Mishra S, Mårtensson C, Ellenrieder L, Priesnitz C, Straub SP, Doan KN, Kulawiak B, Bildl W, Rampelt H, Wiedemann N, Pfanner N, Fakler B, Becker T: Mitochondrial complexome reveals quality-control pathways of protein import. Nature 2023; 614: 153-159.
• Rampelt H, Wollweber F, Licheva M, de Boer R, Perschil I, Steidle L, Becker T, Bohnert M, van der Klei I, Kraft C, van der Laan M, Pfanner, N: Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth. Cell Rep, 2022; 38: 110290.
• Takeda H, Tsutsumi A, Nishizawa T, Lindau C, Busto JV, Wenz LS, Ellenrieder L, Imai K, Straub SP, Mossmann W, Qiu J, Yamamori Y, Tomii K, Suzuki J, Murata T, Ogasawara S, Nureki O, Becker T, Pfanner N, Wiedemann N, Kikkawa M, Endo T: Mitochondrial sorting and assembly machinery operates by β-barrel switching. Nature, 2021; 590: 163-169.
• Rampelt H, Pfanner N: Morpholinos meet mitochondria: targeting organellar gene expression. Cell, 2021; 184: 5693-5695.
• Pfanner N, Warscheid B, Wiedemann N: Mitochondrial proteins: from biogenesis to functional networks. Nat Rev Mol Cell Biol, 2019; 20: 267-284.
• Pfanner N, Zimmermann R, Hartl FU: Walter Neupert (1939–2019). Cell, 2019; 178: 1031-1033.  Reprinted in Mol. Cell, 2019; 75: 661-663.
• Araiso Y, Tsutsumi A, Qiu J, Imai K, Shiota T, Song J, Lindau C, Wenz LS, Sakaue H, Yunoki K, Kawano S, Suzuki J, Wischnewski M, Schütze C, Ariyama H, Ando T, Becker T, Lithgow T, Wiedemann N, Pfanner N, Kikkawa M, Endo, T: Structure of the mitochondrial import gate reveals distinct preprotein paths. Nature, 2019; 575: 395-401. 
• Höhr AIC, Lindau C, Wirth C, Qiu J, Stroud DA, Kutik S, Guiard B, Hunte C, Becker T, Pfanner N, Wiedemann N: Membrane protein insertion through a mitochondrial β-barrel gate. Science, 2018; 359: eaah6834.
• Chatterjee A, Syefferth J, Lucci J, Gilsbach R, Preissl S, Böttinger L, Martensson CU, Panhale A, Stehle T, Kretz O, Sahyoun AH, Avilov S, Eimer S, Hein L, Pfanner N, Becker T, Akhtar A: MOF acetyl transferase regulates transcription and respiration in mitochondria. Cell, 2016; 167: 722-738.
• Rampelt H, Pfanner N: Coordination of two genomes by mitochondrial translational plasticity. Cell, 2016; 167: 308-310.
• Shiota T, Imai K, Qiu J, Hewitt VL, Tan K, Shen HH, Sakiyama N, Fukasawa Y, Hayat S, Kamiya M, Elofsson A, Tomii K, Horton P, Wiedemann N, Pfanner N, Lithgow T, Endo T: Molecular architecture of the active mitochondrial protein gate. Science, 2015; 349, 1544-1548.
• Harbauer AB, Opalinska M, Gerbeth C, Herman JS, Rao S, Schönfisch B, Guiard B, Schmidt O, Pfanner N, Meisinger C: Cell cycle-dependent regulation of mitochondrial preprotein translocase. Science, 2014; 346: 1109-1113.
• 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. Cell, 2013; 154 (3) : 596-608: http://dx.doi.org/10.1016/j.cell.2013.06.033
• Schmidt O, Harbauer AB, Rao S, Eyrich B, Zahedi RP, Stojanovski D, Schonfisch B, Guiard B, Sickmann A, Pfanner N, Meisinger C: Regulation of mitochondrial protein import by cytosolic kinases. Cell, 2011; 144 (2) : 227-239: http://dx.doi.org/10.1016/j.cell.2010.12.015
• Stroud DA, Meisinger C, Pfanner N, Wiedemann N: Biochemistry. Assembling the outer membrane. Science, 2010; 328 (5980) : 831-832: http://dx.doi.org/10.1126/science.1190507

Selected publications 2009 and earlier

• Chacinska A, Koehler CM, Milenkovic D, Lithgow T, Pfanner N: Importing mitochondrial proteins: machineries and mechanisms. Cell, 2009; 138 (4) : 628-644: http://dx.doi.org/10.1016/j.cell.2009.08.005
• Wiedemann N, Meisinger C, Pfanner N: Cell biology. Connecting organelles. Science, 2009; 325 (5939) : 403-404: http://dx.doi.org/10.1126/science.1178016
• Wiedemann N, van der Laan M, Pfanner N: SnapShot: import and sorting of mitochondrial proteins. Cell, 2009; 138 (4) : 808-808.e1: http://dx.doi.org/10.1016/j.cell.2009.08.004
• Vögtle FN, Wortelkamp S, Zahedi RP, Becker D, Leidhold C, Gevaert K, Kellermann J, Voos W, Sickmann A, Pfanner N, Meisinger C: Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability. Cell, 2009; 139: 428-439.
• Kutik, S., Stojanovski, D., Becker, L., Becker, T., Meinecke, M., Krüger, V., Prinz, C., Meisinger, C., Guiard, B., Wagner, R., Pfanner, N., and Wiedemann, N. (2008). Dissecting membrane insertion of mitochondrial β-barrel proteins. Cell 132, 1011-1024.
• Meisinger, C., Sickmann, A., and Pfanner, N. (2008). The mitochondrial proteome: from inventory to function. Cell 134, 22-24.
• 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.
• 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.
• Pfanner, N., Wiedemann, N., and Meisinger, C. (2004). Double membrane fusion. Science 305, 1723-1724.
• Rehling, P., Model, K., Brandner, K., Kovermann, P., Sickmann, A., Meyer, H.E., Kühlbrandt, W., Wagner, R., Truscott, K.N., and Pfanner, N. (2003). Protein insertion into the mitochondrial inner membrane by a twin-pore translocase. Science 299, 1747-1751.
• 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.
• van Wilpe, S., Ryan, M.T., Hill, K., Maarse, A.C., Meisinger, C., Brix, J., Dekker, P.J.T., Moczko, M., Wagner, R., Meijer, M., Guiard, B., Hönlinger, A., and Pfanner, N. (1999). Tom22 is a multifunctional organizer of the mitochondrial preprotein translocase. Nature 401, 485-489.
• Voisine, C., Craig, E.A., Zufall, N., von Ahsen, O., Pfanner, N., and Voos, W. (1999). The protein import motor of mitochondria: unfolding and trapping of preproteins are distinct and separable functions of matrix Hsp70. Cell 97, 565-574.
• Hill, K., Model, K., Ryan, M.T., Dietmeier, K., Martin, F., Wagner, R., and Pfanner, N. (1998). Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins. Nature 395, 516-521.
• Dietmeier, K., Hönlinger, A., Bömer, U., Dekker, P.J.T., Eckerskorn, C., Lottspeich, F., Kübrich, M., and Pfanner, N. (1997). Tom5 functionally links mitochondrial preprotein receptors to the general import pore. Nature 388, 195-200.
• Kiebler, M., Keil, P., Schneider, H., van der Klei, I.J., Pfanner, N., and Neupert, W. (1993). The mitochondrial receptor complex: a central role of MOM22 in mediating preprotein transfer from receptors to the general insertion pore. Cell 74, 483-492.
• Pfanner, N., Rassow, J., van der Klei, I.J., and Neupert, W. (1992). A dynamic model of the mitochondrial protein import machinery. Cell 68, 999-1002.
• Söllner, T., Rassow, J., Wiedmann, M., Schloßmann, J., Keil, P., Neupert, W., and Pfanner, N. (1992). Mapping of the protein import machinery in the mitochondrial outer membrane by crosslinking of translocation intermediates. Nature 355, 84-87.
• Schneider, H., Söllner, T., Dietmeier, K., Eckerskorn, C., Lottspeich, F., Trülzsch, B., Neupert, W., and Pfanner, N. (1991). Targeting of the master receptor MOM19 to mitochondria. Science 254, 1659-1662.
• Söllner, T., Pfaller, R., Griffiths, G., Pfanner, N., and Neupert, W. (1990). A mitochondrial import receptor for the ADP/ATP carrier. Cell 62, 107-115.
• Kiebler, M., Pfaller, R., Söllner, T., Griffiths, G., Horstmann, H., Pfanner, N., and Neupert, W. (1990). Identification of a mitochondrial receptor complex required for recognition and membrane insertion of precursor proteins. Nature 348, 610-616.
• Neupert, W., Hartl, F.-U., Craig, E.A., and Pfanner, N. (1990). How do polypeptides cross the mitochondrial membranes? Cell 63, 447-450.
• Kang, P.-J., Ostermann, J., Shilling, J., Neupert, W., Craig, E.A., and Pfanner, N. (1990). Requirement for hsp70 in the mitochondrial matrix for translocation and folding of precursor proteins. Nature 348, 137-143.
• Söllner, T., Griffiths, G., Pfaller, R., Pfanner, N., and Neupert, W. (1989). MOM19, an import receptor for mitochondrial precursor proteins. Cell 59, 1061-1070.
• Pfanner, N., Orci, L., Glick, B.S., Amherdt, M., Arden, S.R., Malhotra, V., and Rothman, J.E. (1989). Fatty acyl-coenzyme A is required for budding of transport vesicles from Golgi cisternae. Cell 59, 95-102.
• Pfanner, N., Tropschug, M., and Neupert, W. (1987). Mitochondrial protein import: nucleoside triphosphates are involved in conferring import-competence to precursors. Cell  49, 815-823.