February 28, 2007

Researchers at Drexel University College of Medicine have made a key discovery about the mitochondrial functions of the malaria parasite. Their study, published in the March 1 issue of the journal Nature, is a significant step to developing new, more effective anti-malarial drugs, and to understanding mitochondrial evolution as a whole.

Plasmodium falciparum is the deadliest of the four parasites that cause malaria in humans. It kills an estimated one to three million people each year, most of them children living in Africa.  Just as do our own cells, the parasite’s cells contain mitochondria, but there is an important functional difference. In human cells, the mitochondria are the primary site where the oxygen taken in by respiration is consumed to produce usable energy.  Malaria mitochondria, however, do not produce energy yet still consume oxygen.  The question has been for what purpose.

The Drexel team studied the blood stages of P. falciparum and discovered that the parasite’s mitochondrial respiration serves only one function - synthesis of DNA precursors.  The researchers found that adding just one extra enzyme into the malaria parasites using genetic manipulation caused them to become independent of respiration.

“In addition to answering a question of mitochondrial functions in malaria parasites, this helps us understand more clearly the mechanism by which a current anti-malarial drug, Malarone, works. It will also help in the approaches to be taken as cheaper versions of this rather expensive but effective drug are being developed,” said author Akhil Vaidya, PhD, professor of Microbiology and Immunology at Drexel University College of Medicine and director of the college’s Center for Molecular Parasitology. “Drug combinations are critical for treating malaria because of the ever-present danger of resistance development.  Our findings will help guide the type of combinations to be used.”

The study also offers insight into the ongoing evolution of mitochondrial genomes.  These organelles have evolved from bacteria that originally lived inside the ancestral cells. Over time, the size of the genomic DNA of the internal bacteria/mitochondria became greatly reduced. The malarial parasite’s mitochondrial DNA is the smallest known and encodes only three enzymes, all of which are involved in mitochondrial respiration.

“Our findings show that malaria parasites can declare their metabolic independence from mitochondrial respiration by acquiring just one enzyme, and now they should not need mitochondrial DNA.  A similar situation has occurred in some single cell organisms over the evolutionary period; we may be able to achieve this in laboratory,” said Vaidya. 

The research was supported by grants from the National Institute of Allergy and Infectious Diseases.

Complete list of authors is as follows:
Heather J. Painter*, Joanne M. Morrisey*, Michael W. Mather* & Akhil B. Vaidya*

*All are affiliated with:
Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.