{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Cho YK"],"funding":["National Research Foundation of Korea (NRF)","NIDDK NIH HHS","National Research Foundation of Korea"],"pagination":["1113"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12855804"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(1)"],"pubmed_abstract":["Efficient fatty acid (FA) re-esterification is essential for lipid homeostasis in adipocytes, yet the mechanisms coordinating Coenzyme A (CoA) availability at the endoplasmic reticulum (ER)-a major site of lipid synthesis-remain unclear. Here, we identify TMEM120A as an ER-resident CoA-binding protein that regulates intracellular FA metabolism. TMEM120A interacts with the ER-localized acyl-CoA synthetase ACSL1 and ACSL3 to promote long-chain acyl-CoA synthesis and channeling into the ER, thereby facilitating FA re-esterification and lipid cycling during lipolysis. By relieving acyl-CoA-mediated feedback inhibition of lipolysis, TMEM120A enhances lipid turnover while protecting against ER stress and lipotoxicity. Adipocyte-specific deletion of Tmem120a in mice impairs lipolysis-induced energy expenditure and exacerbates inflammation and metabolic dysfunction under high-fat diet conditions. These findings establish TMEM120A as a critical regulator of ER CoA handling and lipid flux, revealing a previously unrecognized mechanism that links intracellular CoA dynamics to systemic energy balance and metabolic health."],"journal":["Nature communications"],"pubmed_title":["TMEM120A maintains adipose tissue lipid homeostasis through ER CoA channeling."],"pmcid":["PMC12855804"],"funding_grant_id":["R01 DK062292","RS-2023-00213572, RS-2024-00400118, RS-2025-16063709"],"pubmed_authors":["Jung CW","Jung YS","Kim JK","Lee J","Mottillo EP","Cho YK","Granneman JG","Shim M","Seomoon C","Kwon SW","Park S","Lee YH","Mai XL","Namgoong S","Jeong YL","Choi YH","Seong JK","Lee DK"],"additional_accession":[]},"is_claimable":false,"name":"TMEM120A maintains adipose tissue lipid homeostasis through ER CoA channeling.","description":"Efficient fatty acid (FA) re-esterification is essential for lipid homeostasis in adipocytes, yet the mechanisms coordinating Coenzyme A (CoA) availability at the endoplasmic reticulum (ER)-a major site of lipid synthesis-remain unclear. Here, we identify TMEM120A as an ER-resident CoA-binding protein that regulates intracellular FA metabolism. TMEM120A interacts with the ER-localized acyl-CoA synthetase ACSL1 and ACSL3 to promote long-chain acyl-CoA synthesis and channeling into the ER, thereby facilitating FA re-esterification and lipid cycling during lipolysis. By relieving acyl-CoA-mediated feedback inhibition of lipolysis, TMEM120A enhances lipid turnover while protecting against ER stress and lipotoxicity. Adipocyte-specific deletion of Tmem120a in mice impairs lipolysis-induced energy expenditure and exacerbates inflammation and metabolic dysfunction under high-fat diet conditions. These findings establish TMEM120A as a critical regulator of ER CoA handling and lipid flux, revealing a previously unrecognized mechanism that links intracellular CoA dynamics to systemic energy balance and metabolic health.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-16T07:09:25.85Z","creation":"2026-06-16T03:09:51.974Z"},"accession":"S-EPMC12855804","cross_references":{"pubmed":["41423633"],"doi":["10.1038/s41467-025-67870-7"]}}