SLC25A36 Inhibitors

Chemical inhibitors of SLC25A36 can effectively disrupt its function by targeting various aspects of mitochondrial metabolism and ATP transport. Bongkrekic Acid and Atractyloside are potent inhibitors of the adenine nucleotide translocase (ANT), which is essential for the exchange of ATP and ADP across the mitochondrial membrane, a process in which SLC25A36 is directly involved. These inhibitors bind to ANT and obstruct its conformational changes, thereby preventing the normal function of SLC25A36 in ATP transport. Carboxyatractyloside serves a similar purpose, locking ANT in an inoperative state which in turn inhibits the action of SLC25A36. Glibenclamide, by inhibiting ATP-sensitive potassium channels, alters the mitochondrial membrane potential and disrupts the electrochemical gradient required for SLC25A36 to carry out its transport functions.

Decylubiquinone, by mimicking coenzyme Q, disrupts the electron transport chain, thereby reducing the proton gradient necessary for SLC25A36 activity. TTFA and Malonate, both acting on different complexes of the electron transport chain, reduce the efficiency of electron transport and the formation of the proton gradient, crucial for the functioning of SLC25A36. Antimycin A and Rotenone, by binding to complex III and inhibiting complex I respectively, prevent the creation of a proton gradient used by SLC25A36 to facilitate ATP/ADP exchange. Oligomycin directly inhibits ATP synthase, leading to a reduction in ATP synthesis and availability, which indirectly inhibits the transport capabilities of SLC25A36 due to a lack of substrate. FCCP dissipates the proton gradient through uncoupling oxidative phosphorylation, rendering SLC25A36 unable to transport ATP effectively due to the loss of its driving force. Lastly, Zinc Pyrithione acts to inhibit the respiratory chain, leading to a decrease in the proton motive force and ATP levels, resulting in the functional inhibition of SLC25A36 within the ATP transport cycle.