Fig. 1

Mitochondria are defective in SMA MNs. a, b Volcano plot (a) and pie chart (b) of whole proteome analysis comparing WT and SMA MNs; plotted p values (−log₁₀) against fold changes (log₂, SMA/WT). Four independent samples of WT MNs and three independent samples of SMA MNs were used for analysis. p values were determined using unpaired two-sided t-test. Proteins with p < 0.05 are highlighted in blue (313 down-regulated) and red (120 up-regulated), and proteins with localization in mitochondria are marked in purple (32 down-regulated and 29 up-regulated). c, d Gene ontology (GO) analysis of 345 down-regulated (c) and 149 up-regulated proteins (d) in SMA MNs. The 5 most significant terms of each category are shown. e Representative images and quantification of mitochondria in 100 μm long primary axons of WT and SMA MNs labeled with anti-Tau antibody (green), DAPI (blue), and anti-TOM20 antibody or MitoTracker (white). Scale bars: 20 µm. Each dot represents the average number of mitochondria in each neuron (n = 30; biological replicates N = 3). Two-way ANOVA with Tukey HSD post hoc analysis was used to determine statistical significance for multiple comparisons. Bar graphs depict the mean ± S.D. ***p < 0.001