# Essential functions of the mitochondrion in malaria parasites

> **NIH NIH DP2** · OHIO STATE UNIVERSITY · 2024 · $459,131

## Abstract

PROJECT SUMMARY
Malaria is a devastating disease that impacts millions of people on an annual basis. While several species
of Plasmodium parasites cause malaria in humans, P. falciparum is responsible for the highest rates of
complications and mortality. Malaria elimination efforts are continually challenged by the emergence and
spread of resistant P. falciparum strains to frontline chemotherapies. New treatments targeting alternative
molecular targets in the parasite are therefore urgently needed. An ideal antimalarial drug should exhibit
prophylactic, curative and transmission blocking properties. However, few clinically approved drugs fit
this profile due to a two-fold problem: 1) many genes that are essential in mosquito or liver stage parasites
are dispensable in symptomatic blood stages, making it hard to identify a drug target that is relevant
throughout the parasite life cycle; 2) the field has historically suffered from a dearth of robust genetic tools
to investigate basic parasite biology, a prerequisite for uncovering novel therapeutic approaches. In
response to these challenges, we propose using new and improved genetic methods to expand the
druggable parasite proteome across all stages of infection. We will focus our efforts on the parasite
mitochondrion, a promising source of drug targets since it is essential in all parasite life stages and is
highly divergent from its human counterpart. This organelle’s potential as an antimalarial target has
already been validated by atovaquone, the only mitochondrial inhibitor in clinical use. Notably,
atovaquone belongs to the very small group of drugs that are active against both symptomatic and
transmission stages of infection. The mitochondrion contains nearly 10% of the total parasite proteome,
the majority of which has no known function. Identifying essential processes within the mitochondrion can
pave the way for the development of new drugs that not only prevent or treat malaria but also block
transmission.

## Key facts

- **NIH application ID:** 10951080
- **Project number:** 1DP2AI184824-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Krithika Rajaram
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $459,131
- **Award type:** 1
- **Project period:** 2024-08-20 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10951080

## Citation

> US National Institutes of Health, RePORTER application 10951080, Essential functions of the mitochondrion in malaria parasites (1DP2AI184824-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10951080. Licensed CC0.

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