Expression of Miro1 rescues axonal transport of mitochondria in ALS mutant SOD1 expressing neurons. (Aa, Ba) Kymographs show transport of mitochondria in rat cortical neurons and motor neurons co-expressing EGFP-SOD1 WT or G93A with empty vector (Ctrl), myc-Miro1 (WT), or Myc-Miro1E208K/E328K (KK). (Ab, c; Bb, c) Quantitative analysis of mitochondrial transport shows that expression of ALS mutant SOD1 significantly impairs overall motility of mitochondria (Ab, Bb—Motile) because of a selective block of anterograde (Ab, Bb—Anterograde), but not retrograde transport (Ab, Bb—Retrograde). As a consequence, SOD1 G93A disturbed the balance of transport to inhibit anterograde and promote retrograde movement (Ac, Bc). Co-expression of myc-Miro1 WT or KK, fully rescued impaired transport of mitochondria (Ab, Bb) and rebalanced anterograde and retrograde transport (Ac, Bc). Results are shown as mean ± SEM, statistical significance was determined by one-way ANOVA followed by Fisher’s LSD test, ns, not significant, * P < 0.05, *** P < 0.001, **** P < 0.0001, N (cortical neurons): SOD1 WT+Ctrl: 18, SOD1 WT+WT: 24, SOD1 WT+KK: 23, SOD1 G93A+Ctrl: 20, SOD1 G93A+WT: 24, SOD1 G93A+KK: 22 from 4 experiments; N (motor neurons) = WT+Ctrl: 15, SOD1 WT+WT: 16, SOD1 G93A+Ctrl: 19, SOD1 G93A+WT: 29 from 5 experiments.