Figure 3. Retinas Can Use Malate to Produce Succinate via Reverse Electron Transport at SDH.

(A) Labeling schematic showing isotopomers of TCA cycle metabolites produced by tissue incubated in U-¹³C-malate + ¹²C-glucose. (B) Isotopomers produced by retinas and eyecups incubated in 5 mM ¹²C-glucose and 5, 50, or 500 μM U-¹³C-malate for 5 min (n = 5 retinas or eyecups per concentration; error bars indicate SEM). (C) Total fumarate levels in retinas and eyecups incubated in 5 mM ¹²C-glucose and 5, 50, or 500 μM U-¹³C-malate for 5 min (n = 5 retinas or eyecups per concentration; error bars indicate SEM; * indicates p < 0.05 using Welch’s t test). (D) m4 fumarate and m4 succinate in retinas supplied with 5 mM ¹²C-glucose + 50 μM U-¹³C-malate in the presence or absence of 20 mM malonate for 5 min (n = 6 retinas; error bars indicate SEM; **** indicates p < 0.0001 using Welch’s t test). (E) m4 fumarate and m4 succinate in WT and AIPL1^−/− retinas supplied with 5 mM ¹²C-glucose + 50 μM U-¹³C-malate for 5 min (n = 6 retinas; error bars indicate SEM; ** indicates p < 0.005 using Welch’s t test). (F) Labeling schematic showing isotopomers produced by 4-²H-glucose. (G) Accumulation of deuterated (m1) malate, fumarate, and succinate α-ketoglutarate in retinas and eyecups incubated in 5 mM 4-²H-glucose for 0.02, 0.5, 1, 2, and 5 min (n = 2 retinas per time point; error bars indicate SEM).