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Pouch's newfound role tied to potential new treatment for malaria

For a century, a tiny compartment called the volutin granule in yeast, fungi and bacteria was thought to be a storage granule with no active function. University of Illinois scientists, however, have found that the granule is really an organelle -- a live vacuole (a subcellular pouch) with a membrane and active enzymes -- and it may provide a new line of attack against malaria.

The researchers began studying the compartment in 1994 with funding from the National Institutes of Health. They labeled the organelle an acidocalcisome in recognition of its acidic and calcium components. They also found that it contains a pyrophosphatase, an enzyme that acts like a pump and allows protons to be transported inside it, and that the organelle has plant-like qualities.

In the April 1 issue of the Biochemical Journal, the researchers reported that the organelle exists in Plasmodium berghei, a malaria-causing organism. The new work -- funded by the Burroughs Wellcome Fund -- involved extensive molecular studies, including immunofluorescence microscopy, in which the organelle of the malaria parasite was compared with those in other parasites and plants.

"These so-called granules are not just storage granules. They have a function," said Roberto Docampo, a professor of veterinary pathobiology in the UI College of Veterinary Medicine. "These organelles have pumps for the uptake of protons to make them acidic, and for the uptake of calcium and other elements. The calcium is not bound permanently. It can be released as free calcium. It is involved in metabolism.

"Since the malaria parasites have this organelle, it means that the polyphosphates and pyrophosphates are important for the organism's existence, and that analogs of these compounds could be used for chemotherapy," Docampo said.

A new weapon against malaria is sorely needed, because the malaria parasite is rapidly becoming resistant to chloroquine, the most commonly used drug against mal
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Contact: Jim Barlow
b-james3@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
30-Apr-2000


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