{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Auger C"],"funding":["NIDDK NIH HHS","Howard Hughes Medical Institute"],"pagination":["1311-1325.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12137002"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["37(6)"],"pubmed_abstract":["Adipose tissue thermogenesis contributes to energy balance via mitochondrial uncoupling protein 1 (UCP1) and UCP1-independent pathways. Among UCP1-independent thermogenic mechanisms, one involves Ca<sup>2+</sup> cycling via SERCA2b in adipose tissue; however, the underlying molecular basis remains elusive. Here, we report that an endoplasmic reticulum (ER) membrane-anchored peptide, C4orf3 (also known as another regulin [ALN]), uncouples SERCA2b Ca<sup>2+</sup> transport from its ATP hydrolysis, rendering the SERCA2b-C4orf3 complex exothermic. Loss of C4orf3/ALN improved the energetic efficiency of SERCA2b-dependent Ca<sup>2+</sup> transport without affecting SERCA2 expression, thereby reducing adipose tissue thermogenesis and increasing the adiposity of mice. Notably, genetic depletion of"],"journal":["Cell metabolism"],"pubmed_title":["Identification of a molecular resistor that controls UCP1-independent Ca&lt;sup&gt;2+&lt;/sup&gt; cycling thermogenesis in adipose tissue."],"pmcid":["PMC12137002"],"funding_grant_id":["DP1 DK126160","R01 DK097441"],"pubmed_authors":["Fujimoto M","Shinoda K","Inaba K","Verkerke ARP","Griffin PR","Stimson RH","Caycedo MPH","Li M","O'Leary TR","Ikeda K","Auger C","Yook JS","Xiaohan C","Kajimura S","Oikawa S"],"additional_accession":[]},"is_claimable":false,"name":"Identification of a molecular resistor that controls UCP1-independent Ca&lt;sup&gt;2+&lt;/sup&gt; cycling thermogenesis in adipose tissue.","description":"Adipose tissue thermogenesis contributes to energy balance via mitochondrial uncoupling protein 1 (UCP1) and UCP1-independent pathways. Among UCP1-independent thermogenic mechanisms, one involves Ca<sup>2+</sup> cycling via SERCA2b in adipose tissue; however, the underlying molecular basis remains elusive. Here, we report that an endoplasmic reticulum (ER) membrane-anchored peptide, C4orf3 (also known as another regulin [ALN]), uncouples SERCA2b Ca<sup>2+</sup> transport from its ATP hydrolysis, rendering the SERCA2b-C4orf3 complex exothermic. Loss of C4orf3/ALN improved the energetic efficiency of SERCA2b-dependent Ca<sup>2+</sup> transport without affecting SERCA2 expression, thereby reducing adipose tissue thermogenesis and increasing the adiposity of mice. Notably, genetic depletion of","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-06-03T07:54:43.244Z","creation":"2026-04-26T03:10:37.099Z"},"accession":"S-EPMC12137002","cross_references":{"pubmed":["40199326"],"doi":["10.1016/j.cmet.2025.03.009"]}}