Fig. 3: Complex I disease mutations reduce levels of NADPH and GSH and cause oxidative stress.
From: Defective NADPH production in mitochondrial disease complex I causes inflammation and cell death
a Relative NADPH levels analyzed by LC-MS, b NADPH/NADP+ ratio, c GSH/GSSG ratio, and d relative reactive oxygen species (ROS) levels measured using dichlorodihydrofluorescein diacetate (H2DCFDA) in sgNeg and sgME1 ND1 mutant cells cultured under glucose or galactose conditions for 48 h (n = 3). e Cell number of galactose-grown ND1 cells (96 h) supplemented with GSH (2 mM), NAC (4 mM), or the indicated doses of MitoQ (n = 3). f–i Growth curves in galactose-grown ND1 cells treated with GSH or NAC. 6-Aminonicotinamide (6-AN) (100 μM) was used to inhibit PPP (n = 3), and g ROS levels, h cell number, and i H2O2-induced cell death was assessed after 48 h in WT cells (n = 3). Experiments are represented as means ± SEM., n > 3 biological replicates. Asterisks denote *p < 0.05, **p < 0.01, or ***p < 0.001. Two-way ANOVA in a–d, g–i and paired two-tailed Student’s t test in e, f. Gluc glucose, Galac galactose. Red dashed lines indicate initial seeding density.
