课题组确定SLC25A45是线粒体TML载体，控制肉毒碱生物合成和燃料转换。SLC25A45缺乏症减少了肉碱池，损害了线粒体脂肪酸氧化，将依赖转移到碳水化合物代谢。SLC25A45缺陷小鼠不耐冷，对GLP1受体激动剂（GLP-1RA）的脂质动员产生抗性，使其抵抗脂肪组织损失。他们的研究表明，线粒体在燃料转换中起着调节检查点的作用，对代谢适应和基于GLP-1RA的抗肥胖治疗的疗效有影响。
据悉，环境适应通常涉及能量利用向线粒体脂肪酸氧化的转变，这需要肉毒碱。除了动物来源的饮食要求外，从三甲基赖氨酸（TML）中生物合成肉毒碱是必不可少的，特别是对于那些以植物为基础的饮食者；然而，其分子调控和生理作用尚不清楚。
附：英文原文
Title: Mitochondrial control of fuel switching via carnitine biosynthesis
Author: Christopher Auger, Hiroshi Nishida, Bo Yuan, Guilherme Martins Silva, Masanori Fujimoto, Mark Li, Daisuke Katoh, Dandan Wang, Melia Granath-Panelo, Jihoon Shin, Rose Witte, Jin-Seon Yook, Anthony R. P. Verkerke, Alexander S. Banks, Sheng Hui, Lijun Sun, Shingo Kajimura
Issue&Volume: 2026-01-08
Abstract: Environmental adaptation often involves a shift in energy utilization toward mitochondrial fatty acid oxidation, which requires carnitine. Besides dietary sources of animal origin, carnitine biosynthesis from trimethyllysine (TML) is essential, particularly for those who consume plant-based diets; however, its molecular regulation and physiological role remain elusive. Here, we identify SLC25A45 as a mitochondrial TML carrier that controls carnitine biosynthesis and fuel switching. SLC25A45 deficiency decreased the carnitine pool and impaired mitochondrial fatty acid oxidation, shifting reliance to carbohydrate metabolism. Slc25a45-deficient mice were cold-intolerant and resistant to lipid mobilization by GLP1 receptor agonist (GLP-1RA), rendering them resistant to adipose tissue loss. Our study suggests that mitochondria serve as a regulatory checkpoint in fuel switching, with implications for metabolic adaptation and the efficacy of GLP-1RA-based anti-obesity therapy.
DOI: ady5532
Source: https://www.science.org/doi/10.1126/science.ady5532