Department Langer

Mitochondrial Proteostasis

Mitochondria are cell organelles that are central to metabolism and perform vital functions. With age, mitochondrial activity decreases, which is associated with numerous age-related diseases. In our research, we investigate the role of mitochondria in cellular ageing. We focus on mitochondrial proteases as drivers of the dynamic behavior and functional plasticity of mitochondria.

Mitochondria are dynamic metabolic organelles that participate in cellular signaling and adapt to varying physiological demands. The activity of mitochondria declines with age and a dysfunction of these organelles is associated with numerous age-associated diseases, raising the question: how do mitochondria influence cell fitness and ageing? The department seeks to define molecular mechanisms that preserve mitochondrial function with age and drive the dynamic adaptation of the mitochondrial proteome in a cell- and tissue-specific manner. Projects focus on the function of mitochondrial proteases that are emerging as central regulators and orchestrate complex interactions of mitochondria with their cellular environment.

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Selected publications

Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7 
Deshwal, S., Onishi, M., Tatsuta, T., Bartsch, T., Cors, E., Ried, K., Lemke, K., Nolte, H., Giavalisco, P., Langer, T.
(2023) Nature Cell Biology

OMA1-mediated integrated stress response protects against ferroptosis in mitochondrial cardiomyopathy
Ahola, S., Rivera Mejías, P., Hermans, S., Chandragiri, S., Giavalisco, P., Nolte, H., Langer, T.
(2022) Cell Metabolism, 34, 11, 1875-1891

Regulation of mitochondrial proteostasis by the proton gradient
Patron, M., Tarasenko, D., Nolte. H., Kroczek, L., Ghosh, M., Ohba, Y., Lasarzewski, Y., Ahmadi, ZA., Cabrera-Orefice, A., Eyiama, A., Kellermann,T., Rugarli, EI., Brandt, U., Meinecke, M., Langer, T.
(2022) EMBO J. 41, 16, e110476

Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity
Sprenger, H.-G., MacVicar, T., Bahat, A., Fiedler, K. U., Hermans, S., Ehrentraut, D., Ried, K., Milenkovic, D., Bonekamp, N., Larsson, N.-G., Nolte, H., Giavalisco, P., Langer, T.
(2021) Nature Metabolism, 3, 5, 636-650

Lipid signaling drives proteolytic rewiring of mitochondria by YME1L
MacVicar, T., Ohba, Y., Nolte, H., Fiona, C. M., 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., Langer, T. 
(2019) Nature 575, 7782, 361–365