DMT1 shows localization to structures associated with vesicular trafficking as well as the digestive vacuole and exhibits differential uptake of [3H]QN between NF54 and Cam3.II variants. a-g, Representative immunofluorescence assays (IFA) showing DMT1-3HA-tagged parasites stained with 𝛼-HA (DMT1, green), DAPI (nuclear, blue), 𝛼-Rab7 (late endosome) (a), 𝛼-Rab5B (early endosome) (b), 𝛼-BiP (ER) (c), 𝛼-PfK13 (ER, vesicles, near cytostome) (d), 𝛼-PfEXP2 (parasitophorous vacuolar membrane) (e), 𝛼-PfCRT (digestive vacuole membrane) (f), or Nile Red (lipid bodies) (g) antibodies, and the 3D volume reconstructions of IFA images. Scale bars: 1 m for IFA (black), 0.5 m for 3D volume reconstructions (white). h,i, Time course of 300 nM [3H]QN and 300 nM [3H]CQ uptake measured with PfCRT (NF54 or Cam3.II), DMT1 (NF54 or Cam3.II), or Band 3-containing proteoliposomes. Data are mean ± SEM of n = 3 independent experiments performed as technical duplicates. Statistical significance between NF54 and Cam3.II variants for each protein was determined by unpaired Student’s t-tests corrected for multiple testing (h, i). *p < 0.05, **p < 0.01, ****p < 0.0001. Kanai M, Mok S, Yeo T, Shears MJ, Ross LS, Jeon JH, Narwal S, Haile MT, Tripathi AK, Mlambo G, Kim J, Gil-Iturbe E, Okombo J, Fairhurst KJ, Bloxham T, Bridgford JL, Sheth T, Ward KE, Park H, Rozenberg FD, Quick M, Mancia F, Lee MCS, Small-Saunders JL, Uhlemann AC, Sinnis P, Fidock DA. Identification of the drug/metabolite transporter 1 as a marker of quinine resistance in a NF54×Cam3.II P. falciparum genetic cross. bioRxiv [Preprint]. 2024 2024.09.27.615529. PMID: 39386571