Research group of Heike Rampelt
Research
Functional Organization of the Mitochondrial Inner Membrane
We investigate the functions and crosstalk of proteins and phospholipids that give rise to the complex architecture, functional asymmetry and dynamics of the mitochondrial inner membrane.
In contrast to the smooth mitochondrial outer membrane, the inner membrane (IM) has an intricate, characteristic morphology that optimally supports oxidative phosphorylation. The IM comprises two subdomains that are topologically and functionally distinct: The flat inner boundary membrane hosts the protein import machinery, while the cristae, tubular or sheet-like membrane folds, harbour the complexes of the respiratory chain. These two subdomains are connected by a narrow, tubular structure with high local membrane curvature, the crista junction, that constitutes a diffusion barrier between the specialized membrane compartments. A conserved IM protein complex, the mitochondrial contact site and cristae organizing system (MICOS), is required to maintain crista junctions and directly induces negative membrane curvature at the crista junction. In recent years, MICOS has emerged as a central hub in an interaction network spanning as diverse functions as protein biogenesis, respiratory chain assembly, phospholipid remodelling and transport, mitochondrial dynamics, and nucleoid inheritance.
Aside from MICOS, several other proteins as well as the non-bilayer forming phospholipids cardiolipin and phosphatidylethanolamine influence the morphology and dynamics of the IM. We study the crosstalk between MICOS and both protein and phospholipid determinants of cristae morphology, for example the communication between MICOS and the F1Fo-ATP synthase: With respect to cristae biogenesis, the F1Fo-ATP synthase performs a role complementing that of MICOS: It imposes positive membrane curvature by forming angular dimer rows that localize to the cristae rims and tips. Consequently, both MICOS and F1Fo-ATP synthase are required to establish native cristae architecture. We have discovered that the MICOS core component Mic10 interacts with dimeric F1Fo-ATP synthase, suggesting that the two complexes might coordinate their activities. This finding is particularly exciting since the mechanisms of cristae biogenesis are practically unknown.
Team
| name | Phone +49 (0) 761 203 | |
|---|---|---|
| Dr. Heike Rampelt | -5245 | heike.rampelt(at)biochemie.uni-freiburg.de |
| Dr. Kuo Song | -5254 | kuo.song(at)biochemie.uni-freiburg.de |
| Patrick Horten | -5237 | patrick.horten(at)biochemie.uni-freiburg.de |
| Inge Perschil | -97475 | inge.perschil(at)biochemie.uni-freiburg.de |
Open positions
We are looking to recruit curious, motivated students for a master or bachelor thesis or a practical course. Please send your application to:
heike.rampelt(at)biochemie.uni-freiburg.de
CV Heike Rampelt
| Group leader, Institute of Biochemistry and Molecular Biology, University of Freiburg | |
| 2013 ‑ 2017 | Postdoctoral research in the lab of Nikolaus Pfanner, Institute of Biochemistry and Molecular Biology, University of Freiburg; funded by a postdoctoral fellowship by the Peter und Traudl Engelhorn Stiftung |
| 2012 | Postdoctoral research in the lab of Bernd Bukau, ZMBH, University of Heidelberg |
| 2011 | Dr. rer. nat. summa cum laude |
| 2006 ‑ 2011 | Doctoral research in the lab of Bernd Bukau, ZMBH, University of Heidelberg, on the interplay of Hsp110 and Hsp70 chaperones; funded by a PhD scholarship of the Boehringer Ingelheim Fund |
| 2005 | Diploma thesis in the lab of Volker Lipka, University of Tübingen, on pathogen-induced polarized vesicle transport in A. thaliana |
| Biochemistry studies at the University of Tübingen; international study year at the University of Toronto, Canada, funded by a DAAD scholarship |
Funding
The Rampelt research group receives research funding from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) within the framework of the Research Unit FOR 2848: Nanoscale Architecture and Heterogeneity of the Mitochondrial Inner Membrane.
Publications
Zerbes RM, Colina-Tenorio L, Bohnert M, von der Malsburg K, Peikert CD, Mehnert CS, Perschil I, Klar RFU, de Boer R, Kram A, van der Klei I, Oeljeklaus S, Warscheid B, Rampelt H, van der Laan M (2025) Coordination of cytochrome bc1 complex assembly at MICOS. EMBO Rep 26, 353-384.
Jia Y, Wang S, Urban S, Müller JM, Sum M, Wang Q, Bauer H, Schulte U, Rampelt H, Pfanner N, Schüle KM, Imhof A, Forné I, Berlin C, Sigle A, Gratzke C, Greschik H, Metzger E, Schüle R (2025) Mitochondrial KMT9 methylates DLAT to control pyruvate dehydrogenase activity and prostate cancer growth. Nat Commun 16, 1191.
Song K, Rampelt H (2024) Isolation of yeast mitochondria by differential centrifugation. Methods Enzymol 706, 3-18.
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 (2024) Identification of MIMAS, a multifunctional mega-assembly integrating metabolic and respiratory biogenesis factors of mitochondria. Cell Rep 43, 113772.
Horten P, Rampelt H (2024) Roles of the F1Fo-ATP synthase and MICOS in mitochondrial membrane organization. In A Reichert (Ed.), The dynamic nature of mitochondria (pp. 3-23). CRC Press.
Schulte U, den Brave F, Haupt A, Gupta A, Song J, et al. (2023) Mitochondrial complexome reveals quality-control pathways of protein import. Nature 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. (2022) Dual role of Mic10 in mitochondrial cristae organization and ATP synthase-linked metabolic adaptation and respiratory growth. Cell Rep. 38, 110290.
Rampelt H, Pfanner, N. (2021) Morpholinos meet mitochondria: Targeting organellar gene expression. Cell 184: 5693-5695.
Horten P, Colina-Tenorio L, Rampelt H. (2020) Biogenesis of mitochondrial metabolite carriers. Biomolecules 10: 1008.
Colina-Tenorio L, Horten P, Pfanner N, Rampelt H. (2020) Shaping the mitochondrial inner membrane in health and disease. J. Intern. Med. 287: 645-664.
Rampelt H, Sucec I, Bersch B, Horten P, Perschil I, Martinou JC, van der Laan M, Wiedemann N, Schanda P, Pfanner N. (2020) The mitochondrial carrier pathway transports non-canonical substrates with an odd number of transmembrane segments. BMC Biol. 18: 2.
Rampelt H, Wollweber F, Gerke C, de Boer R, van der Klei IJ, Bohnert M, Pfanner N, van der Laan M (2018) Assembly of the mitochondrial cristae organizer Mic10 is regulated by Mic26-Mic27 antagonism and cardiolipin. J. Mol. Biol. 430: 1883-1890.
Rampelt H, van der Laan M (2017) The yin and yang of mitochondrial architecture – interplay of MICOS and F1Fo-ATP synthase in cristae formation. Microb. Cell 4: 236-239.
Ellenrieder L, Rampelt H, Becker T (2017) Connection of protein transport and organelle contact sites in mitochondria. J. Mol. Biol. 429: 2148-2160.
Hessenberger M, Zerbes RM, Rampelt H, Kunz S, Xavier AH, Purfürst B, Lilie H, Pfanner N, van der Laan M, Daumke O (2017) Regulated membrane remodeling by Mic60 controls formation of mitochondrial crista junctions. Nat. Commun. 8: 15258.
Rampelt H, Bohnert M, Zerbes RM, Horvath SE, Warscheid B, Pfanner N, van der Laan M (2017) Mic10, a core subunit of the mitochondrial contact site and cristae organizing system, interacts with the dimeric F1Fo-ATP synthase. J. Mol. Biol. 429: 1162-1170.
Rampelt H, Zerbes RM, van der Laan M, Pfanner N (2017) Role of the mitochondrial contact site and cristae organizing system in membrane architecture and dynamics. Biochim. Biophys. Acta 1864: 737-746.
Rampelt H, Pfanner N (2016) Coordination of two genomes by mitochondrial translational plasticity. Cell 167: 308-310.
Bohnert M, Zerbes RM, Davies KM, Mühleip AW, Rampelt H, Horvath SE, Boenke T, Kram A, Perschil I, Veenhuis M, Kühlbrandt W, van der Klei IJ, Pfanner N, van der Laan M (2015) Central role of Mic10 in the mitochondrial contact site and cristae organizing system. Cell Metab. 21: 745-755.
Rampelt H, van der Laan M (2015) Metabolic remodeling: a pyruvate transport affair. EMBO J. 34: 835-837.
Horvath SE, Rampelt H, Oeljeklaus S, Warscheid B, van der Laan M, Pfanner N (2015) Role of membrane contact sites in protein import into mitochondria. Protein Sci. 24: 277-297.
Mehnert CS, Rampelt H, Gebert M, Oeljeklaus S, Schrempp SG, Kochbeck L, Guiard B, Warscheid B, van der Laan M (2014) The mitochondrial ADP/ATP carrier associates with the inner membrane presequence translocase in a stoichiometric manner. J. Biol. Chem. 289: 27352-27362.
Rampelt H, Kirstein-Miles J, Nillegoda NB, Chi K, Scholz SR, Morimoto RI,Bukau B (2012) Metazoan Hsp70 machines use Hsp110 to power protein disaggregation. EMBO J. 31: 4221-4235.
Rampelt H, Mayer MP, Bukau B (2011) Nucleotide Exchange Factors for Hsp70 Chaperones. Methods Mol. Biol. 787: 83-91.
Andréasson C, Rampelt H, Fiaux J, Druffel-Augustin S, Bukau B (2010) The endoplasmic reticulum Grp170 acts as a nucleotide exchange factor of Hsp70 via a mechanism similar to that of the cytosolic Hsp110. J. Biol. Chem.285: 12445-12453.
Andréasson C, Fiaux J, Rampelt H, Druffel-Augustin S, Bukau B (2008) Insights into the structural dynamics of the Hsp110-Hsp70 interaction reveal the mechanism for nucleotide exchange activity. Proc. Natl. Acad. Sci. U S A105: 16519-16524.
Andréasson C, Fiaux J, Rampelt H, Mayer MP, Bukau B (2008) Hsp110 is a Nucleotide-activated Exchange Factor for Hsp70. J. Biol. Chem. 283: 8877-8884.
Sadlish H, Rampelt H, Shorter J, Wegrzyn RD, Andréasson C, Lindquist S, Bukau B (2008) Hsp110 chaperones regulate prion formation and propagation in S. cerevisiae by two discrete activities. PLoS ONE 3: e1763 (2008). doi:10.1371/journal.pone.0001763.
Kwon C, Neu C, Pajonk S, Yun HS, Lipka U, Humphry M, Bau S, Straus M, Kwaaitaal M, Rampelt H, El Kasmi F, Jürgens G, Parker J, Panstruga R, Lipka V, Schulze-Lefert P (2008) Co-option of a default secretory pathway for plant immune responses. Nature 451: 835-840.