# Cofactor metabolism and mitochondrial function in malaria parasites

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $748,716

## Abstract

Plasmodium parasites are responsible for hundreds of millions of malaria cases annually. During the asexual
stages of development in red blood cells, malaria parasites acquire certain nutrients from human serum while
retaining the ability to synthesize others. We are studying an essential enzyme cofactor called lipoate and its
metabolism in Plasmodium falciparum. Our studies demonstrate that erythrocytic stage parasites are
auxotrophic for lipoate, even though they contain a metabolic pathway to synthesize this cofactor. Proteins in
the apicoplast organelle rely on lipoate synthesis while proteins in the parasite mitochondrion rely on
scavenging and cannot obtain lipoate synthesized in the apicoplast. The proposed studies are focused on two
aspects of lipoate scavenging and employ a combination of biochemical, cell biology and genetic approaches.
Our first aim is to define the essentail roles of lipoate-dependent proteins and identify the factors required to
support these activities in the parasite mitochondrion. Our second aim will probe the mechanism of lipoate
uptake and attachment to mitochondrial proteins in order to understand how, when and why this process is
gated by redox potential. These studies will forge a detailed link between the lipoate attachment enzymes and
their protein substrates. By virtue of relying on a host nutrient, these proteins represent a vulnerable aspect of
parasite biology which could be targeted at several levels.

## Key facts

- **NIH application ID:** 10910015
- **Project number:** 5R01AI168183-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Manuel Llinas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $748,716
- **Award type:** 5
- **Project period:** 2023-08-18 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910015

## Citation

> US National Institutes of Health, RePORTER application 10910015, Cofactor metabolism and mitochondrial function in malaria parasites (5R01AI168183-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10910015. Licensed CC0.

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