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B07 - Cell-type specific mitochondrial Ca2+ handling and selective vulnerability to mitochondrial dysfunction in different dopaminergic neuron populations

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.

Latest publications

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.

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. (2017). Imbalance of mitochondrial respiratory chain complexes in the epidermis induces severe skin inflammation. J. Invest Dermatol. doi: 10.1016/j.jid.2017.08.019. [Epub ahead of print] #corresponding author

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.

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.

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.