UNIVERSITÄT ZU KÖLN

Peter Kloppenburg
Institute for Zoology
University of Cologne

E-mail: peter.kloppenburguni-koeln.de
Phone: +49 - 221 / 470 5950
For more information and contact please visit the KLOPPENBURG LAB.

Rudolf Wiesner
Department of Physiology
University Hospital Cologne

E-mail: Rudolf.Wiesneruni-koeln.de
Phone: +49 - 221 / 478 3610
For more information and contact please visit the WIESNER LAB.

Running time within the CRC 1218: 07/2016 - 06/2020
 

Abstract

We aim to understand if and how the different, neuron type specific dependence on mitochondrial Ca2+ handling might contribute to the selective vulnerability of certain neuron types to mitochondrial dysfunction. We will a) analyse how mitochondria contribute to controlling free cytosolic Ca2+ in dopaminergic midbrain neurons of the substantia nigra (SN) vs. the ventral tegmental area (VTA) and b) if cell-type specific differences in mitochondrial Ca2+ handling between these two neuron types might contribute to their differential susceptibility to neurodegeneration caused by mitochondrial dysfunction, as seen in ageing and Parkinson’s disease.

Project-related publications

Ricke, K.M., Paß, T., Kimoloi, S., Fährmann, K., Jüngst, C., Schauss, A., Baris, O.R., Aradjanski, M., Trifunovic, A., Eriksson Faelker, T.M., Bergami, M. and Wiesner, R.J. (2019). Mitochondrial dysfunction combined with high calcium load leads to impaired antioxidant defense underlying the selective loss of nigral dopaminergic neurons. J. Neurosci., pii: 1345-19. doi: 10.1523/JNEUROSCI.1345-19.2019. [Epub ahead of print]

Holzer, T., Probst, K., Etich, J., Auler, M., Georgieva, V.S., Bluhm, B., Frie, C., Heilig, J., Niehoff, A., Nüchel, N., Plomann, M., Seeger, J.M., Kashkar, H., Baris, O.R., Wiesner, R.J. and Brachvogel, B. (2019). Respiratory chain inactivation links cartilage-mediated growth retardation to mitochondrial diseases. J. Cell Biol. 218, 1853-1870.

Benkert, J., Hess, S., Roy, S., Beccano-Kelly, D., Wiederspohn, N., Duda, J., Simons, C., Patil, K., Gaiffulina, A., Mannal, N., Dragicevic, E., Spaich, D., Müller, S., Nemeth, J., Hollmann, H., Deuter, N., Mousba, Y, Kubisch, C., Poetschke, C., Striessnig, J., Pongs, O., Schneider, T., Wade-Martins, R., Patel, S., Parlato, R., Frank, T., Kloppenburg, P., and Liss, B. (2019). Cav2.3 channels contribute to dopaminergic neuron loss in a model of Parkinson’s disease. Nat. Commun. 10, 5094.

Bugiardini, E., Mitchell, A.L., Rosa, I.D., Horning-Do, H.T., Pitmann, A., Poole, O.V., Holton, J.L., Shah, S., Woodward, C., Hargreaves, I., Quinlivan, R., Amunts, A., Wiesner, R.J., Houlden, H., Holt, I.J., Hanna, M.G., Pitceathly, R.D.S., Spinazzola, A. (2019). MRPS25 mutations impair mitochondrial translation and cause encephalomyopathy. Hum. Mol. Genet. 19 Apr 30. pii: ddz093. doi: 10.1093/hmg/ddz093. [Epub ahead of print]

Murru, S., Hess, S., Barth, E., Almajan, E.R., Schatton, D., Hermans, S., Brodesser, S., Langer, T., Kloppenburg, P., Rugarli, E.I. (2019). Astrocyte-specific deletion of the mitochondrial m-AAA protease reveals glial contribution to neurodegeneration. GLIA 67, 1526-1541.

Lubomirov, L.T., Gagov, H., Schroeter, M.M., Wiesner, R.J., and Franko, A. (2019). Augmented contractility of murine femoral arteries in a streptozotocin diabetes model is related to increased phosphorylation of MYPT1. Physiol Rep. 7(3):e13975. doi: 10.14814/phy2.13975.

Quiñones, M., Al-Massadi, O., Folgueira, C., Bremser, S., Gallego, R., Torres-Leal, L., Haddad-Tóvolli, R., García-Caceres, C., Hernandez-Bautista, R., Lam, B.Y.H., Beiroa, D., Sanchez-Rebordelo, E., Senra, A., Malagon, J.A., Valerio, P., Fondevila, M.F., Fernø, J., Malagon, M.M., Contreras, R., Pfluger, P., Brüning, J.C., Yeo, G., Tschöp, M., Diéguez, C, López, M., Claret, M., Kloppenburg, P., Sabio, G., and Nogueiras, R. (2018). p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1. Nat. Commun. 9, 3432.

Timper, K., Paeger, L., Sánchez-Lasheras, C., Varela, L., Jais, A., Nolte, H., Vogt, M.C., Hausen, A.C., Heilinger, C., Evers, N., Pospisilik, J.A., Penninger, J.M., Taylor, E.B., Horvath, T.L., Kloppenburg, P., and Brüning J.C. (2018). Mild Impairment of Mitochondrial OXPHOS Promotes Fatty Acid Utilization in POMC Neurons and Improves Glucose Homeostasis in Obesity. Cell. Rep. 25, 383-397.

Weiland, D., Brachvogel, B., Hornig-Do, H.-T., Neuhaus, J.F.G., Holzer, T., Tobin, D.J., Niessen, C.M., Wiesner, R.J.# and Baris, O.R. (2018). Imbalance of mitochondrial respiratory chain complexes in the epidermis induces severe skin inflammation. J. Invest Dermatol. 138, 132-140. #corresponding author

Paeger, L., Pippow, A., Hess, S., Paehler, M., Klein, A.C., Husch, A., Pouzat, C., Brüning, J.C., Kloppenburg, P. (2017). Energy imbalance alters Ca2+ handling and excitability of POMC neurons. Elife, 6. pii: e25641. doi: 10.7554/eLife.25641.

Ortner, N.J., Bock, G., Dougalis, A., Kharitonova, M., Duda, J., Hess, S., Tuluc P., Pomberger, T., Stefanova, N., Pitterl, F., Ciossek, T., Oberacher, H., Draheim, H.J., Kloppenburg, P., Liss, B., Striessnig, J. (2017). Lower affinity of isradipine for L-Type Ca2+ channels during substantia nigra dopamine neuron-like activity: implications for neuroprotection in Parkinson’s disease. J. Neurosci. 37, 6761-6777.

Kumar, A. Dejanovic, B., Hetsch, F., Semtner, M., Fusca, D., Arjune, S., Santamaria-Araujo, J.A., Winkelmann, A., Ayton, S., Bush, A.I., Kloppenburg, P., Meier, J.C., Schwarz, G., and Belaidi, A.A. (2017). S-sulfocysteine/NMDA receptor-dependent signaling underlies neurodegeneration in molybdenum cofactor deficiency. J. Clin. Invest. 127, 4365-4378.

Schommers, P., Thurau, A., Bultmann-Mellin, I., Guschlbauer, M., Klatt, A.R., Rozman, J., Klingenspor, M., Hrabe de Angelis, M., Alber, J., Gründemann, D., Sterner-Kock, A., and Wiesner, R.J. (2017). Metformin causes a futile intestinal–hepatic cycle which increases energy expenditure and slows down development of a type 2 diabetes-like state. Mol. Metabolism. 6, 737-747.

Neuhaus, J.F.G., Baris, Kittelmann, O. R. A. Becker, K. Rothschild, M.A., and Wiesner, R.J. (2017). Catecholamine metabolism induces mitochondrial DNA deletions and leads to severe adrenal degeneration during aging. Neuroendocrinology 104, 72-84.

Stöckigt, F., Beiert, T., Knappe, V., Baris, O.R., Wiesner, R.J., Clemen, C.S., Nickenig, G., Andrié, R.P. and Schrickel, J.W. (2017): Aging-related mitochondrial dysfunction facilitates the occurrence of serious arrhythmia after myocardial infarction. Biochem. Biophys. Res. Comm. 493, 604-610.

Lehtonen, J. M., Forsstrom, S., Bottani, E., Viscomi, C., Baris, O. R., Isoniemi, H., Hockerstedt, K., Osterlund, P., Hurme, M., Jylhava, J., Leppa, S., Markkula, R., Helio, T., Mombelli, G., Uusimaa, J., Laaksonen, R., Laaksovirta, H., Auranen, M., Zeviani, M., Smeitink, J., Wiesner, R. J., Nakada, K., Isohanni, P., Suomalainen, A. (2016). FGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders. Neurology 87, 2290-2299.

Szczepanowska, K., Maiti, P., Kukat, A., Hofsetz, E., Nolte, H., Senft, K., Becker, C., Ruzzenente, B., Hornig-Do, H.-T., Wibom, R., Wiesner, R.J., Krüger, M. and Trifunovic, A. (2016). CLPP coordinates mitoribosomal assembly through regulation of ERAL1 levels. EMBO J. 35, 2566-2583.

Franko, A., Huypens, P., Neschen, S., Irmler, M., Rozman J., Rathkolb, B., Neff, F., Prehn, C., Dubois, G., Baumann, M., Massinger, R., Gradinger, D., Przemeck, G.K., Repp, B., Aichler, M., Feuchtinger, A., Schommers, P., Stöhr, O., Sanchez-Lasheras, C., Adamski, J., Peter, A., Prokisch, H., Beckers, J., Walch, A.K., Fuchs, H., Wolf, E., Schubert, M., Wiesner, R.J., and Hrabě de Angelis (2016). Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ treated diabetic mice. Diabetes 65, 2540-2552.