fig1

Figure 1. Overview of the mitochondrial determinants of resistance. Some therapeutic drugs promote a shift in metabolism. Drugs like biguanides that target the complex I of mitochondria promote a shift to glycolysis to meet ATP needs. Similarly, glutaminase inhibitors promote cells to switch to oxidative phosphorylation and BRAF protein inhibitors push cells to metabolize glutamine. Mitochondrial FAO contributes to chemoresistance to 5-fluoro-uracil (5FU), Cisplatin and Cytarabine. Increased intracellular ROS induced by enhanced expression of uncoupling proteins (UCPs), electron transport chain (ETC) activity or drug action are also responsible for chemoresistance. In addition to metabolic shifts, therapeutic drugs also elevate the expression of mitochondrial ABC transporters proteins that allow drug efflux and helps to minimize the inhibitory activity of the drug. Bcl-2 family of prosurvival proteins block apoptosis induced by chemotherapeutic drugs. Mitochondrial biogenesis is also induced during therapy-induced stress by elevation of PGC1α