Mitochondrial membrane potential (MMP) (MMP)

The mitochondrial membrane potential (MMP) in Trypanosoma species is a vital electrochemical gradient across the inner mitochondrial membrane that is essential for parasite survival (Vercesi et al., 2006). In the bloodstream form of Trypanosoma brucei, this potential is uniquely maintained by the F1Fo-ATP synthase (Complex V) operating in reverse, which pumps protons out of the matrix at the expense of ATP (Schnaufer et al., 2005). This gradient is indispensable for the import of nuclear-encoded mitochondrial proteins and the regulation of ion homeostasis, particularly calcium (Meehan et al., 2015). Because the maintenance of MMP in certain trypanosome life stages relies on mechanisms distinct from those in mammalian cells, it represents a vulnerable phenotypic target for chemotherapy (Fidalgo & Gille, 2011). Several existing trypanocides, including pentamidine and diminazene, are known to accumulate in the mitochondrion and disrupt this potential, leading to metabolic collapse (Meehan et al., 2015). However, targeting this process requires high selectivity to avoid host mitochondriotoxicity, as the fundamental physics of the membrane potential is conserved across eukaryotes (Vercesi et al., 2006). Experimental compounds like rhodamine derivatives and dequalinium also target this potential by acting as lipophilic cations that accumulate in the negatively charged mitochondrial matrix (Fidalgo & Gille, 2011). Monitoring the MMP using fluorescent dyes like JC-1 or Rhodamine 123 is a standard method for assessing the efficacy of new trypanocidal candidates in phenotypic screens (Vercesi et al., 2006). Overall, while not a single molecular entity, the maintenance of the mitochondrial membrane potential is a validated physiological target for treating African trypanosomiasis and Chagas disease.

Other names

Mitochondrial electrochemical gradientDelta-psi-mMitochondrial proton motive force

Dissipation of the mitochondrial membrane potential and inhibition of mitochondrial bioenergetics