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B02 | Mitochondrial hydrogen peroxide signaling

Jan Riemer
Institute for Biochemistry
Center of Molecular Biosciences, CoMB
University of Cologne

E-mail: jan.riemerSpamProtectionuni-koeln.de
Phone: +49 - 221 / 470 7306
For more information and contact please visit the RIEMER LAB.

Running time within the CRC 1218: 07/2016 - 06/2024.


Hydrogen peroxide (H2O2) is an unavoidable byproduct of aerobic life. It can be beneficial and deleterious depending on its levels and fluxes, and the functional state of the cell. We will investigate H2O2 handling in human cells, its release to the cytosol, the control of release by different mitochondrial and extra-mitochondrial systems and the impact of mitochondrial H2O2 on physiological processes and cellular proteins. Collectively, we will with this project in mammalian cells answer fundamental questions on the where, when and how of mitochondrial H2O2 production and on the role of H2O2 in coordinating mitochondrial function with the rest of the cell.

Project-related publications

Peker, E., Weiss, K., Song, J., Zarges, C., Gerlich, S., Boehm, V., Trifunovic, A., Langer, T., Gehring, N., Becker, T. and Riemer, J. (2023). A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis. J. Cell Biol. 222, e202210019.

Hermeling, J. CW., Herholz, M., Baumann, L., Cores, E.C., Zečić, A., Hoppe, T., Riemer, J., Trifunovic, A. (2022). Mitochondria-originated redox signalling regulates KLF-1 to promote longevity in Caenorhabditis elegans. Redox Biology 2022,  https://doi.org/10.1016/j.redox.2022.102533

Jacobs, L.J., Hoehne, M.N., Riemer, J. (2022). Measuring Intracellular H2O2 in Intact Human Cells Using the Genetically Encoded Fluorescent Sensor HyPer7. Bio-protocol 12 (20).

Bolgi, O., Silva-Garcia, M., Ross, B., Pilla, E., Kari, V., Killisch, M., Spitzner, M., Stark, N., Lenz, C., Weiss, K., Donzelli, L., Gorrell, M.D., Grade, M., Riemer, J., Urlaub, H., Dobbelstein, M., Huber, R., Geiss-Friedlander, R. (2022). Dipeptidyl peptidase 9 triggers BRCA2 degradation and promotes DNA damage repair. EMBO Rep. e54136.

Jacobs, L.J., Riemer, J. (2022). Maintenance of small molecule redox homeostasis in mitochondria. FEBS Lett. doi: 10.1002/1873-3468.

Salscheider, S.L., Gerlich, S., Cabrera-Orefice, A., Peker, E., Rothemann, R.A., Murschall, L.M., Finger, Y., Szczepanowska, K., Ahmadi, Z.A., Guerrero-Castillo, S., Erdogan, A., Becker, M., Ali, M., Habich, M., Petrungaro, C., Burdina, N., Schwarz, G., Klußmann, M., Neundorf, I., Stroud, D.A., Ryan, M.T., Trifunovic, A., Brandt, U., Riemer, J. (2022). AIFM1 is a component of the mitochondrial disulfide relay that drives complex I assembly through efficient import of NDUFS5. The EMBO Journal (2022)e110784. https://doi.org/10.15252/embj.2022110784

Weiss, K., Racho, J., Riemer, J. (2022). Compartmentalized disulfide bond formation pathways. Redox Chemistry and Biology of Thiols, 321-340 (book chapter)

Hoehne, M.N., Jacobs, L.J.H.C., Lapacz, K.J., Calabrese, G., Murschall, L.M., Marker, T., Kaul, H., Trifunovic, A., Morgan, B., Fricker, M., Belousov, V.V., Riemer J. (2022). Spatial and temporal control of mitochondrial H2O2 release in intact human cells. EMBO J, e109169

Gibhardt, C.S., Riemer, J., Bogeski, I. (2022). Calcium and redox signals at mitochondrial interfaces: A nanoview perspective. Cell Calcium 103:102550

Li, X., Straub, J., Medeiros, T.C., Den Brave, F., Peker, E., Atanassov, I., Stillger, K., Michaelis, J.B., Burbridge, E., Adrain, C., Münch, C., Riemer, J., Becker, T., Pernas, L.F. (2022). Mitochondria shed their outer membrane in response to infection-induced stress. Science  • Vol 375, Issue 6577 • DOI: 10.1126/science.abi4343

Murschall, L,M*., Peker, E*., MacVicar, T., Langer, T., Riemer, J. (2021). Protein Import Assay into Mitochondria Isolated from Human Cells. Bio-protocol 11 (12), e4057-e4057

Schlagowski, A.M., Knöringer, K., Morlot, S., Sánchez Vicente, A., Flohr, T., Krämer, L., Boos, F., Khalid, N., Ahmed, S., Schramm, J., Murschall, L.M., Haberkant, P., Stein, F., Riemer, J., Westermann, B., Braun, R.J., Winklhofer, K.F., Charvin, G., Herrmann, J.M. (2021). Increased levels of mitochondrial import factor Mia40 prevent the aggregation of polyQ proteins in the cytosol. EMBO J. e107913

Peker, E., Erdogan, A.J., Volkov, A.N., Riemer, J. (2021). Erv1 and Cytochrome c Mediate Rapid Electron Transfer via A Collision-Type Interaction. J Mol Biol. 433(15):167045

Finger, Y., Habich, M., Gerlich, S., Urbanczyk, S., Logt, E., Koch, J., Schu, L., Lapacz, K.J., Ali, M., Petrungaro, C., Salscheider, S.L., Pichlo, C., Baumann U., Mielenz, D., Brachvogel, B., Hofmann, K., Riemer, J. (2020). Proteasomal degradation induced by DPP9‐mediated processing competes with mitochondrial protein import. EMBO Journal 2020 Aug e103889

Murschall, L.M., Gerhards, A., MacVicar, T., Peker, E., Hasberg, L., Wawra, S., Langer, T., Riemer, J. (2020). The C-terminal region of the oxidoreductase MIA40 stabilizes its cytosolic precursor during mitochondrial import.
DOI: 10.1186/s12915-020-00824-1

Finger, Y., Riemer, J. (2020). Protein import by the mitochondrial disulfide relay in higher eukaryotes. Biol Chem. 2020 May 26;401(6-7):749-763

Szczepanowska, K., Senft, K., Heidler, J., Herholz, M., Kukat, M.A., Höhne, N., Hofsetz, E., Becker, C.,  Kaspar, S., Giese, H., Zwicker, K., Guerrero-Castillo, S, Baumann, L., Kauppila, J., Rumyantseva, A., Müller, S., Frese, C.K., Brandt, U., Riemer, J., Wittig, I., and Trifunovic, A. (2020) A salvage pathway maintains highly functional respiratory complex I. Nature Communications 11, 1643.

Calabrese, G., Peker, E., Amponsah, P.S., Hoehne, M.N., Riemer, T., Mai, M., Bienert, G.P., Deponte, M., Morgan, B., and Riemer, J. (2019). Hyperoxidation of mitochondrial peroxiredoxin limits H2O2-induced cell death in yeast. EMBO J. e101552. doi.org/10.15252/embj.2019101552. [Epub ahead of print]

Habich, M., Salscheider, S.L., Murschall, L.M., Hoehne, M.N., Fischer, M., Schorn, F., Petrungaro, C., Ali, M., Erdogan, A.J., Abou-Eid, S., Kashkar, H., Dengjel, J., and Riemer, J. (2019). Vectorial import via a metastable disulfide-linked complex allows for a quality control step and import by the mitochondrial disulfide relay. Cell Rep. 26, 759-774.

Anton, V., Buntenbroich, I., Schuster, R., Babatz, F., Simões, T., Altin, S., Calabrese, G., Riemer, J., Schauss, A., and Escobar-Henriques, M. (2019). Plasticity in salt-bridge allows fusion-competent ubiquity-lation of mitofusins and Cdc48 recognition. Life Sci. Alliance 2, 2(6). doi: 10.26508/lsa.201900491.

MacVicar, T., Ohba, Y., Nolte, H., Mayer, F.C., Tatsuta, T., Sprenger, H.G., Lindner, B., Zhao, Y., Li, J., Bruns, C., Krüger, M., Habich, M., Riemer, J., Schwarzer, R., Pasparakis, M., Henschke, S., Brüning, J.C., Zamboni, N., and Langer, T. (2019). Lipid signalling drives proteolytic rewiring of mitochondria by YME1L. Nature 575, 361-365.

Roma, L.P., Deponte, M., Riemer, J., and Morgan, B. (2018). Mechanisms and applications of redox-sensitive green fluorescent protein-based hydrogen peroxide probes. Antioxid. Redox Signaling 29, 552-568.

Habich, M., Salscheider, S.L., and Riemer, J. (2018). Cysteine residues in mitochondrial intermembrane space proteins: more than just import. Br. J. Pharmacol. 176, 514-531.

Erdogan, A. J., Ali, M., Habich, M., Salscheider, S. L., Schu, L., Petrungaro, C., Thomas, L. W., Ashcroft, M., Leichert, L. I., Roma, L. P., and Riemer, J. (2018). The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo. Redox Biol. 17, 200-206.

Mattie, S., Riemer, J., Wideman, J.G., McBride, H.M. (2018). A new mitofusin topology places the redox-regulated C terminus in the mitochondrial intermembrane space. J Cell Biol. 217, 507-515.

Meyer, A.J., Riemer, J., and Rouhier, N. (2018). Oxidative protein folding: state-of-the-art and current avenues of research in plants. New Phytol. 221, 1230-1246.

Erdogan, A. J. and  Riemer, J. (2017). Mitochondrial disulfide relay and its substrates: mechanisms in health and disease. Cell Tissue Res. 367, 59-72.

Friederich, M.W., Erdogan, A.J., Coughlin, C.R., Elos, M.T., Jiang, H., O'Rourke, C.P., Lovell, M.A., Wartchow, E., Gowan, K., Chatfield, K.C., Chick, W.S., Spector, E.B., Van Hove, J.L.K., and Riemer, J. (2017). Mutations in the accessory subunit NDUFB10 result in isolated complex I deficiency and illustrate the critical role of intermembrane space import for complex I holoenzyme assembly. Hum. Mol. Genet. 26, 702-716.

Calabrese, G. Morgan, B., and Riemer, J. (2017). Mitochondrial Glutathione: Regulation and Functions. Antioxid. Redox Signaling 27, 1162-1177.

Habich, M. and Riemer, J. (2017). Detection of Cysteine Redox States in Mitochondrial Proteins in Intact Mammalian Cells. In: Mokranjac, D., Perocchi, F. (eds). Mitochondria. Methods in Molecular Biology, Vol 1567. Humana Press, New York, NY.

Döring, K., Ahmed, N., Riemer, T., Suresh, H.G., Vainshtein, Y., Habich, M., Riemer, J., Mayer, M.P., O'Brien, E.P., Kramer, G., and Bukau B. (2017). Profiling Ssb-Nascent Chain Interactions Reveals Principles of Hsp70-Assisted Folding. Cell. 170, 298-311.