Fig. 7: Model of molecular mechanism induced by GL22.

GL22 displayed antitumor activity through mitochondrial dysfunction by inhibiting FABPs. Cardiolipin is a unique phospholipid and almost exclusively exists in the IMM, where cardiolipin is needed for aggregating and anchoring the oxidative phosphorylation proteins, including complexes I, III, and IV. Cardiolipin is synthesized in mitochondria from its basic building blocks, G3P and FAs. More specifically, G3P is acylated to PA in the OMM. PA is translocated from OMM to IMM, and is converted to CL by further acylation. In this pathway, FAs are the donors of all fatty acyl groups. OMM outer mitochondrial membrane, IMM inner mitochondrial membrane, CL cardiolipin, LDs lipid droplets, FA fatty acid, G3P glycero-3-phosphate, PA phosphatidic acid, FABP fatty acid-binding protein, Q coenzyme Q, c cytochrome c; I, II, III, and IV represent electron transport chain complex I, II, III, and IV