Fig. 7: NDI1 restores mitochondrial complex I activity and reduces AIF3 splicing-triggered ROS levels protecting CUX1+ neurons in mice. | Nature Communications

Fig. 7: NDI1 restores mitochondrial complex I activity and reduces AIF3 splicing-triggered ROS levels protecting CUX1+ neurons in mice.

From: AIF3 splicing variant elicits mitochondrial malfunction via the concurrent dysregulation of electron transport chain and glutathione-redox homeostasis

Fig. 7

a NADH dehydrogenase activity of purified AIF, AIF3 and NDI1 with or without electron acceptor UQ1 (100 μM). Data are shown as mean, n = 3 biological replicates. b–d Effects of NDI1 on NADH/NAD+ levels in AIF3 splicing MEFs. n = 4 biological replicates. e Mitochondrial complex I activities in AIF3 splicing and rescue MEFs. n = 4 biological replicates. f–h NADH/NAD+ in the hippocampus of WT and AIF3 splicing (Emx1-Cre + ) mice injected with AAV-GFP or AAV-NDI1. The values of no injection-WT and -AIF3 splicing mice from Fig. 5h-j were used as controls. n = 10 biological replicates. i Mitochondrial complex I activities in the cortex of WT and AIF3 splicing (Emx1-Cre + ) mice injected with AAV-GFP or AAV-NDI1. n = 6 (WT-GFP/AIF3-GFP), 6 (WT-NDI) and 10 (AIF3-NDI) mice. j Mitochondrial ROS levels in AIF3 splicing and rescue MEFs treated with H2O2. n = 3 biological replicates. k, l Nissl staining and quantification of cortical thickness at the identical positions of AIF3 splicing mice (Emx1-cre + ) and their littermates injected with AAV-GFP or AAV-NDI1. n = 27 (WT), 16 (AIF3), 11 (WT-GFP), 14 (AIF3-GFP), 25 (WT-NDI1) and 33 (AIF3-NDI1) images from 4 (WT) and 5 (AIF3) mice/group. m–p Expression (m, n) and quantification (o, p) of CUX1 and NeuN in Emx1-Cre (m) or iCre (n)-induced AIF3 splicing mice and their littermates injected with AAV-GFP or AAV-NDI1. n = 6 mice/group (o) and 15 images/group (p) prepared from 4 WT/WT-NDI1 mice, 3 AIF3 splicing mice, and 6 AIF3-NDI1 mice. q, r NDI1 expression in Emx1-Cre (q) or iCre (r)-induced AIF3 splicing mice and their littermates injected with AAV-GFP or AAV-NDI1. n = 5 (WT) (q), 4 (WT) (r) and 6 (AIF3) (q, r) mice/group. Scale bar, 200 μm (k, m, n, q, r). Data are shown as mean ± S.E.M throughout this figure unless otherwise indicated. One-way ANOVA with Tukey’s multiple comparison test was applied in b-e, and Two-way ANOVA with Tukey’s multiple comparison test was applied in f–j, l, o, p.

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