CHCHD8 Inhibitors

CHCHD8 inhibitors, while not directly targeting the protein, act by disrupting various cellular processes that CHCHD8 depends on for its proper functioning. One of the key mechanisms through which these chemicals act is by impairing mitochondrial function, either through direct inhibition of the electron transport chain components, as seen with rotenone, antimycin A, and sodium azide, or by disrupting the mitochondrial membrane potential and ATP synthesis, as with oligomycin and CCCP. These compounds effectively decrease the energy production within the mitochondria, which is crucial for the maintenance of mitochondrial integrity and function-a process that CHCHD8 is closely associated with.

Furthermore, other compounds like 2-deoxy-D-glucose and paraquat impose metabolic stress either by inhibiting glycolysis or by inducing oxidative stress, respectively. This metabolic stress can have downstream effects on mitochondrial health, thereby affecting CHCHD8 function. Compounds such as tunicamycin and brefeldin A interfere with protein modification and trafficking, essential processes for mitochondrial protein homeostasis, which can indirectly impact CHCHD8's role in these processes.