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. Author manuscript; available in PMC: 2021 Oct 1.
Published in final edited form as: Cell. 2020 Sep 17;183(1):62–75.e17. doi: 10.1016/j.cell.2020.08.039

Figure 3. pH-Gated Secretion of Succinate through MCT1.

Figure 3.

(A) Muscle proteomics identified the MCT transporter family as abundant plasma membrane carboxylic acid transporters in TA and GA muscle.

(B) A model of pH-gated release of the monocarboxylic form of succinate through MCT1.

(C) Depletion of MCT1 inhibits secretion of succinate in C2C12 myotubes initiated by pharmacological acidification. All samples are normalized to the scr. vehicle condition, so siMCT1 does not affect basal succinate release (n = 6).

(D–F) Pharmacological inhibition of MCT1 inhibits secretion of succinate in C2C12 myotubes initiated by pharmacological acidification. All inhibitors were added in parallel with atpenin A5. AZD3965 and AR-C155858 are specific MCT1 inhibitors, whereas α-CHCA inhibits all MCTs (n = 6).

(G) Depletion of MCT1 prevents hypoxic secretion of succinate by C2C12 myotubes (n = 6).

(H) Recombinant human MCT1 facilitates pH-dependent succinate transport in Xenopus oocytes. All rates were obtained in the first 10 min following succinate addition, which corresponds to the linear phase of uptake (n = 6).

(I) Succinate transport by recombinant human MCT1 is inhibited by AZD3965. All rates were obtained in the first 10 min following succinate addition, which corresponds to the linear phase of uptake (n = 5–8).

Data are represented as mean ± SEM. *p or #p < 0.05, **p < 0.01, ***p < 0.005 (two-tailed Student’s t test for pairwise comparisons, one-way ANOVA for multiple comparisons involving one independent variable).