biostudies-literatureAjala INatural Sciences and Engineering Research Council of CanadaCentre d'Excellence en Recherche sur les Maladies Orphelines - Fondation CourtoisRegroupement Québécois de Recherche sur la Fonction, l'Ingénierie et les Applications des Protéines (PROTEO) - Fonds de recherche du Québece70197https://www.ebi.ac.uk/biostudies/studies/S-EPMC12183330biostudies-literatureUnknown34(7)Alternative proteins (AltProts) represent a newly recognized class of biologically active proteins encoded from alternative open reading frames (AltORFs) within already annotated genes. This study focuses on the SLC35A4 gene, which encodes both the reference protein SLC35A4 and the alternative protein AltSLC35A4. Using a combination of microscopy and biochemical analyses, we confirmed the presence of AltSLC35A4 in the inner mitochondrial membrane, resolving previous conflicting reports. Previous studies employing ribosome profiling have revealed that during oxidative stress induced by sodium arsenite, the reference coding sequence of SLC35A4 exhibits the largest increase in translational efficiency among all cellular mRNAs. Our results confirmed this translational upregulation, with the emProtein science : a publication of the Protein SocietyThe dual-coding gene SLC35A4 protects against oxidative stress.PMC12183330RGPIN-2021-03723341121RGPIN‐2021‐03723Lipuma DJmii SAjala ITiaiba IBenlyamani HVanderperre BGrondin BCappadocia LfalseThe dual-coding gene SLC35A4 protects against oxidative stress.Alternative proteins (AltProts) represent a newly recognized class of biologically active proteins encoded from alternative open reading frames (AltORFs) within already annotated genes. This study focuses on the SLC35A4 gene, which encodes both the reference protein SLC35A4 and the alternative protein AltSLC35A4. Using a combination of microscopy and biochemical analyses, we confirmed the presence of AltSLC35A4 in the inner mitochondrial membrane, resolving previous conflicting reports. Previous studies employing ribosome profiling have revealed that during oxidative stress induced by sodium arsenite, the reference coding sequence of SLC35A4 exhibits the largest increase in translational efficiency among all cellular mRNAs. Our results confirmed this translational upregulation, with the em2025-01-01T00:00:00Z2025 Jul2026-04-25T03:28:09.802Z2026-04-25T03:22:13.796ZS-EPMC121833304054571110.1002/pro.70197