Mitochondrial control of fuel switching via carnitine biosynthesis

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…

• CA
  Charles A. King Trust
• NI
  National Institutes of Health

  Awards: DK097441, OD028635, R56DK140139, DK138529, DK126160
• JS
  Japan Society for the Promotion of Science