{"doi":"10.1101/2023.12.31.573776","title":"Mitochondrial choline import regulates purine nucleotide pools via SLC25A48","abstract":"ABSTRACT Choline is an essential nutrient for cellular metabolism, including the biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism. A critical step of choline catabolism is the mitochondrial import and synthesis of chorine-derived methyl donors, such as betaine. However, the underlying mechanisms and the biological significance of mitochondrial choline catabolism remain insufficiently understood. Here, we report that a mitochondrial inner-membrane protein SLC25A48 controls mitochondrial choline transport and catabolism in vivo . We demonstrate that SLC25A48 is highly expressed in brown adipose tissue and required for whole-body cold tolerance, thermogenesis, and mitochondrial respiration. Mechanistically, choline uptake into the mitochondrial matrix via SLC25A48 facilitates betaine synthesis and one-carbon metabolism. Importantly, cells lacking SLC25A48 exhibited reduced synthesis of purine nucleotides and failed to initiate the G1-to-S phase transition, thereby leading to cell death. Taken together, the present study identified SLC25A48 as a mitochondrial carrier that mediates choline import and plays a critical role in mitochondrial respiratory capacity, purine nucleotide synthesis, and cell survival. Key points SLC25A48 is required for mitochondrial choline uptake. Mitochondrial choline uptake regulates one-carbon contribution to purine nucleotide synthesis. Brown fat thermogenesis requires mitochondrial choline catabolism for respiratory capacity. Cancer cells require mitochondrial choline uptake for cell survival.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485824,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":286561,"name":"Xu Shi","orcid":"0000-0002-9473-0359","position":1,"is_corresponding":false},{"id":848443,"name":"Ichitaro Abe","orcid":"0000-0002-2769-5338","position":2,"is_corresponding":false},{"id":268751,"name":"Robert E. Gerszten","orcid":"0000-0002-6767-7687","position":3,"is_corresponding":false},{"id":34059,"name":"Shingo Kajimura","orcid":"0000-0003-0672-5910","position":4,"is_corresponding":false},{"id":646282,"name":"Anthony R.P. Verkerke","orcid":"0000-0002-6198-4723","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:07:52.536246Z","pmid":"38260464","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}