The Use and Abuse of Haem in Apicomplexan Parasites. -
The Use and Abuse of Haem in Apicomplexan Parasites.
Antioxid Redox Signal. 2012 Feb 9;
Authors: van Dooren G, Kennedy A, McFadden G
Abstract
Significance. Haem is an essential prosthetic group for most life on Earth. It functions in numerous cellular redox reactions, including in antioxidant defences and at several stages of the electron transport chain in prokaryotes and eukaryotic mitochondria. Haem also functions as a sensor and transport molecule for gases such as oxygen. Haem is a complex organic molecule and can only be synthesised through a multi-enzyme pathway from simpler precursors. Most free-living organisms synthesise their own haem by a broadly conserved metabolic pathway. Parasites are adept at scavenging molecules from their hosts, and haem is no exception. Recent Advances. In this review we examine recent advances in understanding haem usage and acquisition in Apicomplexa, a group of parasites that include the causative agents of malaria, toxoplasmosis and several major parasites of livestock. Critical Issues. Haem is critical to the survival of Apicomplexa, although the functions of haem in these organisms remain poorly understood. Some Apicomplexa likely scavenge haem from their host organisms, while others retain the ability to synthesise haem. Surprisingly, some Apicomplexa may be able to both synthesise and scavenge haem. Several Apicomplexa live in intracellular environments that contain high levels of haem. Since haem is toxic at high concentrations, parasites must carefully regulate intracellular haem levels and develop mechanisms to detoxify excess haem. Indeed, drugs interfering with haem detoxification serve as major antimalarials. Future Directions. Understanding haem requirements and regulation in apicomplexan parasites promises to reveal multiple targets for much-needed therapeutic intervention against these parasites.
PMID: 22320355 [PubMed - as supplied by publisher] [PubMed-Malaria]