A08 | Regulation of mitochondrial fission factor (MFF) in metabolic homeostasis
Jens Brüning
Max Planck Institute for Metabolism Research
Cologne
Phone: +49 221 / 4726 202
E-mail: Bruening
sf.mpg.de
For more information and contact please visit the BRÜNING LAB
Running time within the CRC 1218: 07/2016 - 06/2024.
From 2016-2020 together with Tamas Horvath, Yale University, Department of Comparative Medicine, New Haven, CT; for more information and contact please visit the HORVATH LAB.
Abstract
In recent studies, we have defined MFF as a novel target which is posttranslationally modified upon sensory food perception to prime postprandial adaptation of liver metabolism and which is also regulated during excessive lipid storage in obesity, resulting in mitochondrial fragmentation. The aim of the current project is to study the role of MFF in metabolic homeostasis through metabolic characterization of conditional MFF-knock-out mice, by investigating the kinase network which is activated upon sensory food perception and by unraveling the physiological role of MFF phosphorylation in inducible mouse models which lack crucial phosphorylation sites.
Project-related publications
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 (2021), https://doi.org/10.1016/j.cmet.2021.10.004
Aravamudhan, S., Türk, C., Bock, T., Keufgens, L., Nolte, H., Lang, F., Krishnan, R.K., König, T., Hammerschmidt, P., Schindler, N., Brodesser, S., Rozsivalova, D.H., Rugarli, E., Trifunovic, A., Brüning, J., Langer, T., Braun, T., Krüger, M. (2021). Phosphoproteomics of the developing heart identifies PERM1 - An outer mitochondrial membrane protein. 2021 Feb 5;154:41-59. doi.org/10.1016/j.yjmcc.2021.01.010
Timper, K., del Río-Martín, A., Cremer, A.L., Bremser, S., Alber, J. Giavalisco, P. Varela, L., Heilinger, C., Nolte, H., Trifunovic, A. Horvath, T.L., Kloppenburg, P., Backes, H. Brüning, J.C. (2020). GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function. Cell Metab. S1550-4131(20)30240-0. doi: 10.1016/j.cmet.2020.05.001. Online ahead of print.
Hammerschmidt, P., Ostkotte, D., Nolte, H., Gerl, M.J., Jais, A., Brunner, H.L., Sprenger, H.G., Awazawa, M., Nicholls, H.T., Turpin-Nolan, S.M., Langer, T., Krüger, M., Brügger, B., and Brüning, J.C. (2019). CerS6-derived sphingolipids interact with Mff and promote mitochondrial fragmentation in obesity. Cell 177, 1536-1552.
Raichur, S., Brunner, B., Bielohuby, M., Hansen, G., Pfenninger, A., Wang, B., Brüning, J.C., Larsen, P.J., and Tennagels, N. (2019). The role of C16:0 ceramide in the development of obesity and type 2 diabetes: CerS6 inhibition as a novel therapeutic approach. Mol. Metab. 21, 36-50.
Turpin-Nolan, S.M., Hammerschmidt, P., Chen, W., Jais, A., Timper, K., Awazawa, M., Brodesser, S., and Brüning, J.C. (2019). CerS1-Derived C18:0 Ceramide in Skeletal Muscle Promotes Obesity-Induced Insulin Resistance. Cell Rep. 26, 1-10.
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., 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.
Brandt, C., Nolte, H., Henschke, S., Engström, Ruud, L., Awazawa, M., Morgan, D.A., Gabel, P., Sprenger, H.G., Hess, M.E., Günther, S., Langer, T., Rahmouni, K., Fenselau, H., Krüger, M., and Brüning, J.C. (2018). Food Perception Primes Hepatic ER-Homeostasis via Melanocortin-Dependent Control of mTOR-Activation. (2018) Cell Nov 15;175, 1321-1335.
Steculorum S.M., Paeger, L., Bremser, S., Evers, N., Hinze, Y., Idzko, M., Kloppenburg, P., and Brüning, J.C. (2015). Hypothalamic UDP increases in obesity and promotes feeding via P2Y6-dependent activation of AgRP-neurons. Cell 162, 1404-1417.
Dietrich, M.O., Zimmer, M.R., Bober, J., and Horvath, T.L. (2015). Hypothalamic Agrp neurons drive stereotypic behaviors beyond feeding. Cell 160, 1222-1232.