Groupleader: Michael Meinecke

Biological membranes exhibit function-related shapes, leading to a plethora of complex and beautiful cell and cell organellar morphologies. Most if not all of these structures have evolved for a particular physiological reason. The shapes of these structures are formed by physical forces that operate on membranes. To create particular shaped cells and cell organelles, membranes must undergo deformations which are determined by the structure and elasticity of the membrane and this process is most probable driven by proteins, lipids and/or interplay of both. Therefore, an important question of current cell biology in conjunction with physics and mathematics is to elucidate the functional cause for these different membrane morphologies as well as how they are formed.
One of the most peculiar membrane shapes is observed in mitochondria. These organelles are surrounded by two membranes and especially the convoluted inner membrane displays a complex ultra-structure. A molecular understanding of how this membrane is shaped is missing to a large extent. Major structure giving elements of the inner membrane are the so-called cristae junctions. This short, tubular membrane segments connect the flat inner boundary membrane with the morphological dynamic cristae membranes. Cristae junctions are rather uniform with inner diameters between 15 – 35 nm and hence display high degrees of membrane curvature. They are thought to be important for cellular physiology as they help to maintain specific protein composition of inner membrane sub-domains. They are further implicated to play a major role during the intrinsic apoptotic pathway. Here, cristae junctions need to open to mobilize cytochrome c that is usually stored in intra-cristae spaces. Understanding how cristae junctions are formed and maintained or in other words, unraveling the molecular mechanisms of membrane remodeling at cristae junctions, is therefore of utmost importance. Unlike membrane remodeling in classical curvature-dependent processes like clathrin-mediated endocytosis, cristae junctions are most likely shaped by integral membrane proteins. At least some of these proteins are likely to be found within the MICOS complex (mitochondrial contact site and cristae organizing system). In recent years we were able to identify two inner membrane proteins that are part of the MICOS, with the ability to bend membranes at cristae junctions

2021-	Professor for Biochemistry and Molecular Biology at Heidelberg University Biochemistry Center (BZH) Medical Faculty
2017-2021	Professor of Membranebiochemistry at the Department of Cellular Biochemistry, University Medical Center Göttingen
2013-2017	Juniorporfessor of Molecular Membrane Biology at the Department of Biochemistry II, University Medical Center Göttingen
2012-2013	Independent group leader at the Department of Biochemistry II, University Medical Center Göttingen
2008–2012	Postdoctoral fellow, MRC - Laboratory of Molecular Biology, Cambridge, UK
2007	Dr. rer. nat. University of Osnabrück

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Hrd1 forms the retrotranslocation pore regulated by auto-ubiquitination and binding of misfolded proteins. (2020) Vasic V., Denkert N., Schmidt C., Riedel D., Stein A., Meinecke M. Nature Cell Biology 22(3):274-281

Atg21 organizes Atg8 lipidation at the contact of the vacuole with the phagophore. (2020) Munzel L., Neumann P., Otto F.B., Krick R., Metje-Sprink J., Kroppen B., Karedla N., Enderlein J., Meinecke M., Ficner R., Thumm M. Autophagy https://doi.org/10.1080/15548627.2020.1766332

PI(4,5)P₂-dependent regulation of exocytosis by amisyn, the vertebrate-specific competitor of synaptobrevin 2. (2020) Kondratiuk I., Jakhanwal S., Jin J., Sathyanarayanan U., Kroppen B., Pobbati A.V., Krisko A., Ashery U., Meinecke M., Jahn R., Fasshauer D., Milosevic I. PNAS https://doi.org/10.1073/pnas.1908232117
  JASSY - a Chloroplast Outer Membrane Protein Required for Jasmonate Biosynthesis. (2019) Guan L., Denkert N., Eisa A., Lehmann M., Sjuts I., Weiberg A, Soll J., Meinecke M., Schwenkert S. PNAS 116, 10568-10575
  The MICOS component Mic60 displays a conserved membrane-bending activity that is necessary for normal cristae morphology. (2017) Tarasenko D., Barbot M., Jans D.C., Kroppen B., Sadowski B., Heim G., Möbius W., Jakobs S., Meinecke M. Journal of Cell Biology 216, 889-899

Cation selectivity of the presequence translocase channel Tim23 is crucial for efficient protein import. (2017) Denkert N., Schendzielorz A.B., Barbot M., Versemann L., Richter F., Rehling P., Meinecke M. ELife pii: e28324. doi: 10.7554/eLife.28324
  Epsin N-terminal homology domain (ENTH) activity as a function of membrane tension. (2016) Gleisner M., Kroppen B., Fricke C., Kliesch T.T., Janshoff A., Meinecke M.*, Steinem C.* Journal of Biological Chemistry 291, 19953-19961 (*corresponding authors)

Reconstitutions of mitochondrial inner membrane remodeling. (2016) Barbot M., Meinecke M. Journal of Structural Biology 196, 20-28 Mic10 oligomerizes to bend mitochondrial inner membranes at cristae junctions. (2015) Barbot M, Jans D, Schulz C, Denkert N, Kroppen B, Hoppert M, Jakobs S, Meinecke M. Cell Metabolism 5, 756-763

Distinct pores for peroxisomal import of PTS1 and PTS2 proteins. (2015) Montilla-Martinez M, Beck S, Meinecke M, Schliebs W, Wagner R, Erdmann R. Cell Reports 13, 2126-2134

Peroxisomal Protein Import Pores. (2015) Meinecke M*, Bartsch P, Wagner R. BBA Molecular Cell Research 1863(5), 821-827 (*corresponding author) Driving a Planar Model System into the 3rd Dimension: Generation and Control of Curved Pore-Spanning Membrane Arrays. (2014) Gleisner M, Mey I, Barbot M, Dreker C, Meinecke M, Steinem C. Soft Matter 10, 6228-6236 Cooperative recruitment of Dynamin and BAR domain-containing proteins leads to GTP-dependent membrane scission. (2013) Meinecke M*, Boucrot E, Camdere G, Hon WC, Mittal R, McMahon HT.* Journal of Biological Chemistry 288, 6651-6661 (*corresponding authors)

Preferential targeting of mitotic cells by Salmonella reveals that cell surface cholesterol is maximal during metaphase. (2013) Santos AJM, Meinecke M, Fessler MB, Holden DW, Boucrot E. Journal of Cell Science 126, 2990-2996 The channel-forming Sym1 protein is transported by the TIM23 complex in a presequence-independent manner. (2012) Reinhold R, Krüger V, Meinecke M, Schulz C, Schmidt B, Guiard B, Wiedemann N, van der Laan M, Wagner R, Rehling P. Molecular and Cellular Biology 32, 5009-5021

The mitochondrial Oxa1 insertase forms a membrane pore in lipid bilayers. (2012) Krüger V, Deckers M, Hildenbeutel M, van der Laan M, Hellmers M, Dreker C, Preuss M, Herrmann JM, Rehling P, Wagner R, Meinecke M. Journal of Biological Chemistry 287, 33314-33326

Impacts of the osmolality and the luminal ionic strength on osmosensory transporter ProP in proteoliposomes. (2012) Culham DE, Meinecke M, Wood JM. Journal of Biological Chemistry 287, 27813-27822

Helicobacter pylori VacA: A new perspective on an invasive chloride channel. (2012) Rassow J, Meinecke M. Microbes and Infection 14, 1026-1033 The Peroxisomal Importomer Constitutes a Large and Highly Dynamic Pore. (2010) Meinecke M, Cizmowski C, Schliebs W, Krüger V, Beck S, Wagner R, Erdmann R. Nature Cell Biology 12, 273 – 277

FCHo proteins are nucleators of clathrin-mediated endocytosis. (2010) Henne WH, Boucrot E, Meinecke M, Evergren E, Vallis Y, Mittal R, McMahon HT. Science 328, 1281-1284

Helicobacter pylori VacA Toxin/Subunit p34: Mitochondrial Targeting of a Proapoptotic Anion Channel. (2010) Domańska G*, Motz C*, Meinecke M*, Harsman A, Papatheodorou P, Reljic B, Dian-Lothrop EA, Galmiche A, Kepp O, Becker L, Günnewig K, Wagner R, Rassow J. PLoS Pathogens 6(4): e1000878. Doi:10.1371/ppat.1000878 (*authors contributed equally to this work) Bacterial Porin Disrupts Mitochondrial Membrane Potential and Sensitizes Host Cells to Apoptosis. (2009) Kozjak-Pavlovic V*, Dian EA.*, Meinecke M*, Kepp O*, Ross K, Rajalingam K, Harsman A, Hauf E, Brinkmann V, Herrmann I, Günther D, Hurwitz R, Rassow J, Wagner R, Rudel T. PLoS Pathogens 5(10): e1000629. doi:10.1371/journal.ppat.1000629 (*authors contributed equally to this work) The Mitochondrial β-Signal and Protein Sorting. (2008) Kutik S, Stojanovski D, Becker T, Stoud DA, Becker L, Meinecke M, Krüger V, Prinz C, Guiard B, Wagner R, Meisinger C, Pfanner N, Wiedemann N. Cell 135, 1159-1160

Dissecting membrane insertion of mitochondrial beta-barrel proteins. (2008) Kutik S, Stojanovski D, Becker L, Becker T, Meinecke M, Krüger V, Prinz C, Meisinger C, Guiard B, Wagner R, Pfanner N, Wiedemann N. Cell 132, 1011-1024 Motor-free mitochondrial presequence translocase drives membrane integration of preproteins. (2007) van der Laan M, Meinecke M, Dudek J, Hutu DP, Lind M, Perschil I, Guiard B, Wagner R, Pfanner N, Rehling P. Nature Cell Biology 9, 1155-1159 Tim50 Maintains the Permeability Barrier of the Mitochondrial Inner Membrane. (2006) Meinecke M, Wagner R, Kovermann P, Guiard B, Mick DU, Hutu DP, Voos W, Truscott K, Chacinska A, Pfanner N, Rehling P. Science 312, 1523-1526

	Finally, we could all sit together in one room and celebrate the end of an exciting year. Good times with our lovely lab neighbours from the Moser group. A warm welcome to our two new PhD students Marina and Dexin. We are very happy to have you.
	Fereshteh is now Dr. Sadeqi. We are proud of her and happy she joined us in Heidelberg.
	One of our last labmeetings in Göttingen. Daryna, Tanaj and Indrani you are missed in Heidelberg. Pouya we hope to see you soon.

	Mariam Barbot | Mari was our first PhD student. She identified Mic10 as a membrane remodeling protein that bends membranes at crista junctions. She works now as a science and technology expert at Novartis.
	Niels Denkert | Niels did his PhD and a PostDoc in our group. Together with the Stein lab he could identify Hrd1 as the first ubiquitin-gated membrane pore. He also showed that the ion-selectivity of Tim23 is an important feature of it's substrate recognition. Niels now is an intellectual property manager.
	Benajmin Kroppen | Ben was a PhD student in our group. He could show that the membrane remodeling activity of the ENTH domain of epsin1 is regulated by protein-protein and protein-membrane interactions. Ben is now a staff scientist at NanoTag Biotechnologies.
	Indrani Mukherjee | Indrani did her PhD thesis in our group where she worked towards an understanding of how Mic10 and Mic60 affect physiological parameters of mitochondria. Indrani works at ChromoTek in Munich now.
	Daryna Tarasenko | Daryna did her PhD thesis with us and stayed on as a PostDoc for a couple of years. Daryna showed that membrane curvature induction by Mic60 is an ancient mechanism already found in alpha proteobacteria. She now works with CureVac.

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