Extended Data Fig. 3: Piericidin A inhibits mitochondrial complex I.

a) Schematic of the mitochondrial ETC, indicating forward and reverse (RET) electron transport. Piericidin A inhibits mitochondrial complex I, preventing proton pumping, superoxide production, and both forward and reverse electron transport. b) OCR in BMDMs after 1-hour treatment with or without 100 nM or 500 nM piericidin A (N = 8 basal; N = 4 100 nM; N = 6 500 nM). c) NAD⁺/NADH ratio in BMDMs after 4-hour treatment with or without LPS (100 ng/mL), with or without piericidin A (500 nM) (N = 4 for each condition). d) Heatmap of significantly altered metabolites in BMDMs treated with piericidin A (500 nM) with or without LPS (100 ng/mL) for 4 hours. The relative abundance of each metabolite is depicted as z score across rows (red, high; blue, low). (N = 5 for each condition). e) Succinate concentration (AU, arbitrary units) in WT BMDMs with or without treatment with LPS (100 ng/mL), with or without piericidin A (500 nM) for 4 hours (N = 5, for each condition). Data are means + /− SEM. * p < 0.05, one-way ANOVA with Tukey test for multiple comparisons (b *p < 0.0001; c *p = 0.0442 UT/Piericidin A, *p = 0.0426 LPS/LPS + Piericidin A; e *p = 0.0258 UT/LPS, *p = 0.0043 LPS/LPS + Piericidin), or one-way ANOVA with Fisher’s LSD (d). Parts of this figure were created with BioRender.com.

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