Mitochondrial choline import regulates purine nucleotide pools via SLC25A48.
Mitochondrial choline import regulates purine nucleotide pools via SLC25A48.
复制标题
线粒体胆碱输入通过 SLC25A48 调节嘌呤核苷酸库。
DOI：
10.1101/2023.12.31.573776
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Kajimura,Shingo
中科院分区：
文献类型：
--
作者：
Verkerke,AnthonyRP;Shi,Xu;Abe,Ichitaro;Gerszten,RobertE;Kajimura,Shingo
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.
