{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kumar A"],"funding":["BLRD VA","NIDDK NIH HHS","NHLBI NIH HHS"],"pagination":["eadt6366"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12466849"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(39)"],"pubmed_abstract":["The lysosome integrates anabolic signaling and nutrient sensing to regulate intracellular growth pathways. The leucine-rich repeat-containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signaling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes. We show that LRRC8A affects leucine-stimulated mTOR; lysosome size; number; pH; expression of lysosomal proteins LAMP2, P62, and LC3B; and lysosomal function. Mutating an LRRC8A lysosomal targeting dileucine motif sequence (LRRC8A-L706A;L707A) in myotubes recapitulates the abnormal AKT signaling and altered lysosomal morphology and pH observed in LRRC8A knockout cells. In viv"],"journal":["Science advances"],"pubmed_title":["Lysosomal LRRC8 complex impacts lysosomal pH, morphology, and systemic glucose metabolism."],"pmcid":["PMC12466849"],"funding_grant_id":["R01 HL108379","R01 DK127080","R01 HL107594","P30 DK020579","R01 DK126068","I01 BX004235","K08 HL163469","R01 DK106009","I01 BX005981","R01 HL168600","I01 BX005065","R01 DK115791","I01 BX005072"],"pubmed_authors":["Liu H","Tranter JD","Meyer G","Hong J","Abel ED","Xie L","Hinton A","Feng E","Xu H","Norris AW","Zhao Y","Diwan A","Grueter CE","Sah R","Mikami RT","Abraham N","Henry KM","Hu M","Chadda R","Kumar A","Rawnsley DR"],"additional_accession":[]},"is_claimable":false,"name":"Lysosomal LRRC8 complex impacts lysosomal pH, morphology, and systemic glucose metabolism.","description":"The lysosome integrates anabolic signaling and nutrient sensing to regulate intracellular growth pathways. The leucine-rich repeat-containing 8 (LRRC8) channel complex forms a lysosomal anion channel and regulates PI3K-AKT-mTOR signaling, skeletal muscle differentiation, growth, and systemic glucose metabolism. Here, we define the endogenous LRRC8 subunits localized to a subset of lysosomes in differentiated myotubes. We show that LRRC8A affects leucine-stimulated mTOR; lysosome size; number; pH; expression of lysosomal proteins LAMP2, P62, and LC3B; and lysosomal function. Mutating an LRRC8A lysosomal targeting dileucine motif sequence (LRRC8A-L706A;L707A) in myotubes recapitulates the abnormal AKT signaling and altered lysosomal morphology and pH observed in LRRC8A knockout cells. In viv","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T21:36:35.26Z","creation":"2026-05-02T03:07:39.791Z"},"accession":"S-EPMC12466849","cross_references":{"pubmed":["41004571"],"doi":["10.1126/sciadv.adt6366"]}}