Authors

Discussion

Bloodstream Trypanosoma brucei lives in its host’s blood and its metabolism is reduced, adapted to such a nourishing environment. However, several studies recently found these parasites in additional tissues, such as the adipose tissue or skin. We present here a signalling pathway which would contribute to quick adaptation of metabolism when transferring from blood to a glucose depleted environment. Baker et al. (2015) observed that depletion of vacuolar ATPase (vATPase) enables loss of the kinetoplast, hence loss of subunit A6 of F_OF₁-ATPase, leading to F_OF₁-ATPase uncoupling. In contrast to most other organisms, the canonical function of mitochondrial ATPase (F_OF₁-ATPase) in bloodstream T. brucei is to sustain mitochondrial membrane potential at the expense of ATP, which is mainly produced in glycolysis. Under specific conditions (or in dyskinetoplastic trypanosomes) F_O and F₁ moieties are separated and F_OF₁-ATPase becomes uncoupled losing its function. We propose that a signalling pathway is present and dependent upon glucose availability, leading via vATPase towards F_OF₁-ATPase; depletion of glucose leads to disassembly of vATPase, which further triggers uncoupling of F_OF₁-ATPase. Inhibitors of glucose transport do indeed render the kinetoplast dispensable, as predicted