The importance of the mitochondrial ATP synthase to the survival of the malaria parasite

点击翻译按钮获取中文摘要

Despite several decades of research, with 300 to 500 million new infections and over 1 million deaths, malaria is still one of the world most deadly diseases. Single-celled eukaryotic parasites belonging to the genus Plasmodium are the causative agent of malaria. This parasite shows a rather complex life cycle, which begins with the uptake of the parasite into an Anopheles mosquito during a blood meal on an infected host. After several developmental steps Plasmodium parasites reach the mosquitos salivary glands and are injected into a new host during the next blood meal. Inside the mammalian host the parasite infects liver cells and develops within them without causing any clinical symptoms. Every parasite formes several thousands of so called merozoites, which are released into the bloodstream. These merozoites then invade red blood cells, which marks the beginning of clinical symptoms. Early biochemical tests have shown that during the blood stage the malaria parasite covers its ATP requirements almost solely by glycolysis with oxidative phosphorylation not being needed at this stage. Our preliminary data however shows that the ATP synthase, the key enzyme for ATP production through oxidative phosphorylation, is expressed during the blood stage. We will apply reverse genetics to shed light on this and other contradictive data on the mitochondrial ATP synthase of Plasmodium. We will also expand our studies to the malaria mosquito- and liver stage. The results of this research project could reveal the ATP synthase as a valid drug target as well as the starting point for the development of a vaccine against malaria.