Monocarboxylate transporter (MCT/SLC16) facilitates mammalian mitochondrial lactate transport for energy metabolism
Lactate was traditionally viewed as a mere byproduct of glucose metabolism, but recent research has revealed its crucial role as an energy source for vital organs such as the liver, heart, and brain. Additionally, lactate functions as a signaling molecule that affects cell fate and gene expression. Notably, emerging evidence shows that lactate can enter mitochondria, where it fuels the tricarboxylic acid (TCA) cycle. Yet, despite the well-established presence of intracellular lactate pools, the identity of the mitochondrial lactate transporter in mammals has remained elusive, hindering our grasp of lactate metabolism's implications for various diseases. To investigate this, we utilized a fluorescence lifetime lactate biosensor targeted to the mitochondrial matrix, confirming lactate's entry into mammalian mitochondria. Proteomic analysis identified a subset of monocarboxylate transporters (MCTs/SLC16) located within the mitochondria. We also revealed the involvement of MCTs in the regulation of energy metabolism. This discovery highlights the essential role of MCTs in mitochondrial lactate import, resolving long-standing questions and enhancing our understanding of lactate biology.