Fig. 7

Metabolic reprograming in dermatomyositis. The scheme highlights the primary flux of energy provision pathways in the muscle of normal and DM patients. In normal muscle, most of the glucose taken up by the cell is oxidized in mitochondria to generate a high yield of ATP by oxidative phosphorylation. Mitochondrial activity also generates a little amount of reactive oxygen species (ROS) in the respiratory chain. In contrast, in muscle cells of DM patients glucose is partially oxidized in the cytoplasm to generate metabolic intermediates by the blockage imposed on the glycolytic pathway by the overexpression of the less active PKM2 isoform. Moreover, the overexpression of IF1 in mitochondria also limits cellular ATP availability enforcing aerobic glycolysis and enhancing the production of reactive oxygen species (ROS). Diversion of the glycolytic flux by blockade of glycolysis and oxidative phosphorylation provides the metabolic intermediates that become precursors for the biosynthesis of the macromolecules required for cellular proliferation. In addition, PKM2 can translocate into the nucleus and activates the transcription of several genes involved in cancer development [34–37]. Likewise, the IF1-mediated inhibition of the H⁺-ATP synthase generates a ROS signal that activates in the nucleus programs involved in proliferation, cell death resistance and invasion [38–44]. Thus, the concurrent increase of PKM2 and IF1 expression in the muscle of DM patients leads to metabolic rewiring and ROS signaling that are hallmarks of the oncogenic phenotype