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. 2021 Feb 25;296:100469. doi: 10.1016/j.jbc.2021.100469

Figure 6.

Figure 6

Drp1KO, but not hAPP expression, reduces mitochondria-derived ATP at synapses more than at cell bodies. Drp1KO and control neurons, with or without mutant hAPP, were cotransfected with an ATP-based FRET sensor (ATP1.03YEMK) (49). A, when forced to rely on mitochondria for ATP (acute absence of glucose, addition of glycolytic inhibitors 2-deoxyglucose (2DG) and iodoacetate (IAA); orange horizontal bar), Drp1KO neurons with or without hAPP had only slightly decreased ATP levels at the cell body after stimulation (10 Hz ∗ 60 s, blue horizontal bars). B, in contrast, Drp1KO neurons with or without hAPP had markedly reduced ATP levels at the synapse under these conditions. hAPP did not affect ATP levels. n = 6–12 coverslips/group (with 67–105 boutons and 15–22 cells per group), compilation of four experiments. C and D, To estimate basal ATP consumption, we simultaneously blocked glycolytic production with 2DG and IAA and respiration with oligomycin (oligo). Rates of consumption, assessed in the absence of electrical stimulation, did not differ across groups at the cell body (C) or the synapse (D), as indicated by the initial slope of decline in ATP level. n = 6–8 coverslips/group (with 56–68 boutons and 6–10 cells per group), compilation of three experiments. Data are means ± S.E.M.; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001 control versus Drp1KO (black) and hAPP versus hAPP Drp1KO (red) by two-way ANOVA with repeated measures and Holm–Sidak test.