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Huntingtin protein (Htt) is ubiquitously expressed and it is localized in several organelles, including endosomes. HD is associated with a failure in energy metabolism and oxidative damage. Ascorbic acid is a powerful antioxidant highly concentrated in the brain where it acts as a messenger, modulating neuronal metabolism. It is transported into neurons via the sodium\u2010dependent vitamin C transporter 2 (SVCT2). During synaptic activity, ascorbic acid is released from glial reservoirs to the extracellular space, inducing an increase in SVCT2 localization at the plasma membrane. Here, we studied SVCT2 trafficking and localization in HD. SVCT2 is decreased at synaptic terminals in YAC128 male mice. Using cellular models for HD (STHdhQ7 and STHdhQ111 cells), we determined that SVCT2 trafficking through secretory and endosomal pathways is altered in resting conditions. We observed Golgi fragmentation and SVCT2\/Htt\u2010associated protein\u20101 mis\u2010colocalization. Additionally, we observed altered ascorbic acid\u2010induced calcium signaling that explains the reduced SVCT2 translocation to the plasma membrane in the presence of extracellular ascorbic acid (active conditions) described in our previous results. Therefore, SVCT2 trafficking to the plasma membrane is altered in resting and active conditions in HD, explaining the redox imbalance observed during early stages of the disease.<\/jats:p>","DOI":"10.1002\/jnr.24693","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T02:10:55Z","timestamp":1596593455000},"page":"223-235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Impaired intracellular trafficking of sodium\u2010dependent vitamin C transporter 2 contributes to the redox imbalance in Huntington\u2019s disease"],"prefix":"10.1002","volume":"99","author":[{"given":"Adriana","family":"Covarrubias\u2010Pinto","sequence":"first","affiliation":[{"name":"Instituto de Bioqu\u00edmica y Microbiolog\u00eda Facultad de Ciencias Universidad Austral de Chile Valdivia Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra 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