Fig. 2

Mitochondria in MS CD4⁺ T cells. CD4⁺ T cells boost the expression of glucose transporter (GLUT)1, resulting in enhanced glucose uptake and lactate generation, which can be blocked by 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) inhibitors. The deletion of acetyl-CoA carboxylase 1 (ACC1) reduces the synthesis of de novo fatty acids, decreases IFN-γ⁺ Th17 via the glycolytic-lipogenic pathway, and increases Foxp3⁺ Treg. Pentanoate acts on acetyl-CoA through the mTOR pathway, leading to increased glucose oxidation, secretion of IL-10, and inhibition of IL-17A production. Oleic acid restores the inhibitory state of CD4⁺ to Treg by promoting fatty acid β-oxidation. Pik3c3 increasing and Nur77 deleting both contribute to the elevation of mitochondrial extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Upregulation of mEF-G1 caused electron transport chain (ETC) assembly in mitochondria, and then elevated NAD⁺/NADH ratio. Above three mechanisms enhance Th1 or Th17 differentiation. Additionally, increased mitochondrial ROS can promote Th17 differentiation. Upregulated mitochondrial oxidative phosphorylation (OXPHOS) influences basic leucine zipper transcription factor TF-like (BATF), promoting Th17 differentiation and inhibiting Treg differentiation. DMF as well as the Bim and Bad pathways of phospholipids (PLs) treatment induces increased apoptosis by augmenting mitochondrial ROS production