胆碱是磷脂、神经递质和一碳代谢生物合成的必需营养素，关键步骤是将其导入线粒体。然而，其潜在机制和生物学意义仍然知之甚少。在这里，我们报道了 SLC25A48，一种以前未表征的线粒体内膜载体蛋白，控制线粒体胆碱转运和胆碱衍生甲基供体的合成。我们发现 SLC25A48 是棕色脂肪产热、线粒体呼吸和线粒体膜完整性所必需的。通过 SLC25A48 进入线粒体基质的胆碱促进了甜菜碱和嘌呤核苷酸的合成，而 SLC25A48 的缺失导致线粒体活性氧的产生增加和线粒体脂质失衡。值得注意的是，SLC25A48 基因上携带单核苷酸多态性的人类细胞和缺乏 SLC25A48 的癌细胞表现出线粒体胆碱输入减少、氧化应激增加和细胞增殖受损。总之，这项研究表明 SLC25A48 调节线粒体胆碱分解代谢、生物能量学和细胞存活。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Choline is an essential nutrient for the biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism with a critical step being its import into mitochondria. However, the underlying mechanisms and biological significance remain poorly understood. Here, we report that SLC25A48, a previously uncharacterized mitochondrial inner-membrane carrier protein, controls mitochondrial choline transport and the synthesis of choline-derived methyl donors. We found that SLC25A48 was required for brown fat thermogenesis, mitochondrial respiration, and mitochondrial membrane integrity. Choline uptake into the mitochondrial matrix via SLC25A48 facilitated the synthesis of betaine and purine nucleotides, whereas loss of SLC25A48 resulted in increased production of mitochondrial reactive oxygen species and imbalanced mitochondrial lipids. Notably, human cells carrying a single nucleotide polymorphism on the SLC25A48 gene and cancer cells lacking SLC25A48 exhibited decreased mitochondrial choline import, increased oxidative stress, and impaired cell proliferation. Together, this study demonstrates that SLC25A48 regulates mitochondrial choline catabolism, bioenergetics, and cell survival.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.