|Umbrasas Danielius, Vanagas T, Cizas P, Borutaite V (2019) Itaconic acid decreases mitochondrial respiration and ROS generation in brain tissue. MitoFit Preprint Arch doi:10.26124/mitofit:ea19.MiPSchool.0001.|
Abstract: Version 1 (v1) 2019-06-03 doi:10.26124/mitofit:ea19.MiPSchool.0001
Itaconic acid (IA) is a recently discovered mammalian metabolite which is produced by macrophages upon pro-inflammatory activation: in quiescent bone marrow – derived macrophages (BMDMs). IA is hardly detectable but upon lipopolysaccharide (LPS) stimulation it reaches millimolar concentrations . Recently reported physiological roles of IA include inhibition of bacterial enzyme isocitrate lyase (bactericidal activity) and the inhibition of a Krebs cycle enzyme succinate dehydrogenase (SDH) in the host cells (which has been shown for BMDMs) [2,3]. By inhibiting SDH, IA regulates succinate (a pro-inflammatory metabolite) levels thus remodelling the host cells metabolism during inflammation . Microglia are macrophages residing in the brain, however, it is not clear whether these cells can also produce IA. In general, there has been very little research on IA effects on brain tissue. Therefore, in this study, we investigated whether IA exerts an effect on brain mitochondrial respiration and ROS generation and whether IA is neurotoxic.
• Bioblast editor: Iglesias-Gonzalez J
- Meiser J, Kraemer L, Jaeger C, Madry H, Link A, Lepper PM, Hiller K, Schneider JG (2018) Itaconic acid indicates cellular but not systemic immune system activation. Oncotarget;9(63):32098-32107.
- Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, Binz T, Wegner A, Tallam A, Rausell A, Buttini M, Linster CL, Medina E, et al. (2013) Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci U S A.; 110:7820–5.
- Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma X, Huang SC, Griss T, Weinheimer CJ, Khader S, Randolph GJ, et al. (2016) Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metab; 24:158–66.
- Gnaiger E., Kuznetsov A.V., Schneeberger S., Seiler R., Brandacher G., Steurer W., Margreiter R. (2000) Mitochondria in the Cold. In: Heldmaier G., Klingenspor M., editors. Life in the Cold. Springer; Heiderlberg, Germany: pp. 431–442.
Preprints for Gentle Science