Fig. 4: MFSD1 is a dipeptide uniporter.
From: MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes
a, Combined TEVC and pHin recording of oocytes expressing both MFSD1–GLMP and PQLC2 (sorting mutant L290A/L291A) at their surface. His, but not Lys–Ala, applied at pH 5.0, induces intracellular acidification (orange dotted lines). The traces are representative of five oocytes shown in Extended Data Fig. 3b. b, A model for the acidification induced by His following its release from PQLC2. c, Combined TEVC and pHin recording of an MFSD1–GLMP oocyte perfused with the indicated dipeptides (10 mM) at pH 5.0. d, A model accounting for the selective acidification by His-containing dipeptides. e, The experiment in c was repeated on four MFSD1–GLMP oocytes. The data are means ± s.e.m. of the acidification and current responses normalized to His–Ala (two-tailed unpaired t-test). *P ≤ 0.05, **P ≤ 0.01 and ***P ≤ 0.001. f, Normalized acidification/current ratios provide the number of protons released per translocated elementary charge for each substrate (two-tailed unpaired t-test). Mean ± s.e.m. **P ≤ 0.01 and ***P ≤ 0.001. g, A model accounting for the high number of protons released by His–Glu. At the tested potential (−40 mV), His–Glu molecules would be taken up by MFSD1–GLMP predominantly in the minor cationic form, His+–Glu0, releasing two protons per elementary charge. The higher acidification/current ratio observed (2.5 ± 0.2) may result either from the non-linear acidification/current relationship (Main) or from simultaneous uptake in the predominant zwitterionic form, His+–Glu-, which would release another proton in an electroneutral manner. The source numerical data are available in the source data.
