A06 - Langer

A06 - Mitochondrial YME1L at the interface of cell death and inflammation

Thomas Langer

Max Planck Institute for Biology of Ageing
Contact: langer(at)age.mpg.de
For more information visit: Langer Lab

Abstract

Mitochondria play an active role in cell death control and are emerging as central regulators of innate immunity. In addition to their well-described role in apoptosis, mitochondria have also been linked to other modes of regulated cell death, such as necroptosis, ferroptosis and pyroptosis. This project will examine how the mitochondrial i-AAA protease YME1L regulates cell survival, mtDNA release and inflammatory responses on a molecular level and how this relates to neurodegeneration and tissue-specific cell death in vivo. These studies will help define the role of mitochondria at the interface between cell death and inflammation.

Recent Publications

2023

Deshwal, S., Onishi, M., Tatsuta, T., Bartsch, T., Cors, E., Ried, K., Lemke, L., Nolte, H., Giavalisco, P. & Langer, T. (2023) Mitochondria regulate intracellular coenzyme Q transport and ferroptotic resistance via STARD7. Nat Cell Biol (2023). https://doi.org/10.1038/s41556-022-01071-y

2022

Ahola, S., Rivera Mejías, P., Hermans, S., Chandragiri, S., Giavalisco, P., Nolte, H., Langer, T. (2022) OMA1-mediated integrated stress response protects against ferroptosis in mitochondrial cardiomyopathy. Cell Metabolism Vol 34, Issue 11, 1.11.22 pages 17845-1891.e7 https://doi.org/10.1016/j.cmet.2022.08.017

2021

Willenborg, S., Sanin, D.E., Jais, A., Ding, X.,Ulas, T., Nüchel, J., Popović, M., MacVicar, T., Langer, T., Schultze, J.L., Gerbaulet, A., Roers, A., Pearce, E.J., Brüning, J.C., Trifunovic, A., Eming, S.A. (2021) Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing. Cell Metabolism 33,1–17 December 7, 2021. https://doi.org/10.1016/j.cmet.2021.10.004

Bahat, A., MacVicar, T., and Langer, T. (2021) Metabolism and Innate Immunity Meet at the Mitochondria.

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) Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity. Nature Metabolism 26.04.2021 https://doi.org/10.1038/s42255-021-00385-9

Project related Publications

2013 - 2019

Sprenger, H.G., Wani, G., Hesseling, A., König, T., Patron, M., MacVicar, T., Ahola, S., Wai, T., Barth, E., Rugarli, E.I., Bergami, M., and Langer, T. (2019). Loss of the mitochondrial i-AAA protease YME1L leads to ocular dysfunction and spinal axonopathy. EMBO Mol. Med. 11, e9288.

Saita, S., Nolte, H., Fiedler, K.U., Kashkar, H., Venne, A.S., Zahedi, R.P., Krüger, M., and Langer, T. (2017). PARL mediates Smac proteolytic maturation in mitochondria to promote apoptosis. Nat Cell Biol 19, 318-328.

Korwitz, A., Merkwirth, C., Richter-Dennerlein, R., Troder, S.E., Sprenger, H.G., Quiros, P.M., Lopez-Otin, C., Rugarli, E.I., and Langer, T. (2016). Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria. J Cell Biol 212, 157-166.

Wai, T., Saita, S., Nolte, H., Müller, S., König, T., Richter-Dennerlein, R., Sprenger, H.G., Madrenas, J., Mühlmeister, M., Brandt, U., Krüber, M., and Langer, T. (2016). The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the i-AAA protease YME1L. EMBO Rep 17, 1844-1856.

MacVicar, T., and Langer, T. (2016). OPA1 processing in cell death and disease - the long and short of it. J Cell Sci 129, 2297-2306.

Wai, T., Garcia-Prieto, J., Baker, M.J., Merkwirth, C., Benit, P., Rustin, P., Ruperez, F.J., Barbas, C., Ibanez, B.*, and Langer, T.* (2015). Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. Science 350, aad0116.* co-senior authorship.

Quiros, P.M., Langer, T., and Lopez-Otin, C. (2015). New roles for mitochondrial proteases in health, ageing and disease. Nat Rev Mol Cell Biol 16, 345-359.

Anand, R., Wai, T., Baker, M.J., Kladt, N., Schauss, A.C., Rugarli, E., and Langer, T. (2014). The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J Cell Biol 204, 919-929.

Baker, M.J., Lampe, P.A., Stojanovski, D., Korwitz, A., Anand, R., Tatsuta, T., and Langer, T. (2014). Stress-induced OMA1 activation and autocatalytic turnover regulate OPA1-dependent mitochondrial dynamics. EMBO J 33, 578-593.

Potting, C., Tatsuta, T., König, T., Haag, M., Wai, T., Aaltonen, M.J., and Langer, T. (2013). TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid. Cell Metab 18, 287-295.

Universität zu Köln

Sonderforschungsbereich 1403