title: The proliferating cell hypothesis: a metabolic framework for Plasmodium growth and development.
abstract: We hypothesise that intraerythrocytic malaria parasite metabolism is not merely fulfilling the need for ATP generation, but is evolved to support rapid proliferation, similar to that seen in other rapidly proliferating cells such as cancer cells. Deregulated glycolytic activity coupled with impaired mitochondrial metabolism is a metabolic strategy to generate glycolytic intermediates essential for rapid biomass generation for schizogony. Further, we discuss the possibility that Plasmodium metabolism is not only a functional consequence of the 'hard-wired' genome and argue that metabolism may also have a causal role in triggering the cascade of events that leads to developmental stage transitions. This hypothesis offers a framework to rationalise the observations of aerobic glycolysis, atypical mitochondrial metabolism, and metabolic switching in nonproliferating stages.
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
authors.forename: J Enrique
authors.initials: JE
authors.lastname: Salcedo-Sora
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK; Warwick Systems Biology Centre, Senate House, University of Warwick, Coventry, CV4 7AL, UK.
authors.forename: Eva
authors.initials: E
authors.lastname: Caamano-Gutierrez
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ward
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Electronic address: Biagini@liv.ac.uk.
authors.forename: Giancarlo A
authors.initials: GA
authors.lastname: Biagini
mesh_terms: D000332:Aerobiosis; D000818:Animals; D049109:Cell Proliferation; D006019:Glycolysis; D006790:Host-Parasite Interactions; D006801:Humans; D008018:Life Cycle Stages / Q000502:physiology; D010961:Plasmodium / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*
keywords: Warburg effect; dormancy; epigenetics; gametocytes; glycolysis; malaria