Hans-Georg Sprenger

Max Planck Institute for Biology of Ageing

Research Areas

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Molecular Metabolism and Energy Homeostasis

Maintaining energy homeostasis is critical to protect against age-associated diseases. In our lab we study exercise and use models of metabolic diseases to identify and understand the underlying molecular mechanisms ensuring energy homeostasis.

Research Focus

Mitochondria are cellular compartments controlling many metabolic pathways important to ensure functioning of these networks and maintain energy homeostasis. Functional mitochondria are vital for enabling our metabolism to adapt to varying environmental conditions, such as diet, physical activity, or stress. As we age, mitochondrial function and the capacity of our metabolism to adjust to these changing conditions decline, leading to disruptions in energy balance and contributing to age-related metabolic disorders. However, exercise training can significantly enhance mitochondrial function, reshape metabolism, and help prevent or mitigate many chronic diseases associated with aging, ultimately promoting a longer, healthier life. Despite these insights, our understanding of the precise molecular mechanisms involved remains incomplete.

Using exercise as a platform has great potential to identify unknown molecular mechanisms of how our body adapts to stress and prevents age-associated diseases.

Our Goals

Ergothioneine accumulates in muscle mitochondria with exercise training and boosts mitochondrial function. (A) Ergothioneine level in muscle mitochondria isolated from sedentary and mice with 4 weeks access to running wheels. (B) Oxygen consumption rates of C2C212 myotubes upon incubation with ergothioneine.

The goal of our research group is to identify unknown molecular mechanisms controlling mitochondrial function, thereby maintaining energy homeostasis, and protecting against age-related decline. To achieve this goal, we study mitochondrial metabolism in response to exercise and during age-associated metabolic diseases in different cell types in vivo and in cultured cells. We are interested in the role of small molecules such as ergothioneine and ketone bodies during these processes and study how they regulate mitochondrial function and energy homeostasis on the molecular level.

Through this research, we aim to deepen our understanding of the fundamental cellular processes that facilitate adaptation to changes in environmental conditions and metabolic stress. Our goal is also to lay the groundwork for applying these insights to prevent and treat age-related diseases.

Key Publications

  1. Ergothioneine boosts mitochondrial respiration and exercise performance via direct activation of MPST. Sprenger, H.-G., Mittenbühler, M. J., Sun, Y., Van Vranken, J. G., Schindler, S., Jayaraj, A., Khetarpal, S., Vargas-Castillo, A., Puszynska, A. M., Spinelli, J. B., Armani, A., Kunchok, T., Ryback, B., Seo, H.-S., Song, K., Sebastian, L., O’Young, C., Braithwaite, C., Dhe-Paganon, S., Burger, N., Mills, E., Gygi, S. P., Arthanari, H., Chouchani, E. T., Sabatini, D. M., Spiegelman, B.M. (2024) bioRxiv
     
  2. Isolation of extracellular fluids reveals novel secreted bioactive proteins from muscle and fat tissues. Mittenbühler, M. J., Jedrychowski, M. P., Van Vranken, J. G., Sprenger, H.-G., Wilensky, S., Dumesic, P. A., Sun, Y., Tartaglia, A., Bogoslavski, D., A, M., Xiao, H., Blackmore, K. A., Reddy, A., Gygi, S. P., Chouchani, E. T., Spiegelman, B. M. (2023) Cell Metabolism
     
  3. Fumarate is a terminal electron acceptor in the mammalian electron transport chain. Spinelli, J. B., Rosen, P. C., Sprenger, H.-G., Puszysnka, A. M., Mann, J. L., Roessler, J. M., Cangelosi, A. L., Henne, A., Condon, K. J., Zhang, T., Kunchok, T., Lewis, C. A., Chandel, N. S., Sabatini, D. M. (2021) Science
     
  4. Cellular nucleotide imbalance triggers mitochondrial DNA-dependent innate immunity. Sprenger, H.-G., MacVicar, T., Bahat, A., Fiedler, K. U., Hermans, S., Ehrentraut, D., Milenkovic, D., Bonekamp, N., Larsson, N.-G., Nolte, H., Giavalisco, P., Langer, T.  (2021) Nature Metabolism
     
  5. Loss of the mitochondrial i-AAA protease YME1L leads to ocular dysfunction and spinal axonopathy. Sprenger, H.-G., Wani, G., Hesseling, A., König, T., Patron, M., MacVicar, T., Ahola, S., Wai, T., Barth, E., Rugarli, E. I., Bergami, M., Langer, T.
    (2019) EMBO Molecular Medicine

Research Areas

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