Figure 1.

Itaconate inhibited SDH activity in primary cortical neurons. A) Intracellular itaconate levels increased after exposure to 2 mM exogenous itaconate for 2 h. B) Exogenous itaconate drove succinate accumulation while the other metabolites were not affected. Cells were exposed to 2 mM of exogenous itaconate for 2 h. C) Oxygen consumption rate in primary cortical neurons exposed to 2 mM itaconate significantly decreased compared to untreated cells. D) Succinate driven respiration (complex II) in permeabilized primary cortical neurons administered 5 mM succinate and 0.5 μM rotenone. Addition of 5 mM itaconate decreased the oxygen consumption rate. E) Schematic depicting itaconate as a metabolic inhibitor for succinate dehydrogenase (SDH) regulating ROS production upon reperfusion. Data are represented as box (25th to 75th percentile with median line) and whiskers (min. to max. values) with three (A and B) or means ± s.e.m. with 6 biological replicates (C and D). All of the experiments were repeated three independent times with similar results, with the exception of C, which was performed once with 6 biological replicates. Student's t-test with ****P < 0.0001.