# Mitochondrial Functions in Malaria Parasites

> **NIH NIH R01** · DREXEL UNIVERSITY · 2024 · $625,728

## Abstract

Project Summary
The emergence of eukaryotes from an exclusively prokaryotic biosphere, a momentous event that charted a
divergent course for life on Earth, coincided with symbiotic adoption of mitochondria. The complexity of
eukaryotes could not have existed and evolved but for the energy economy supported by mitochondrial
physiology. Given the strong evidence for the monophyletic origin of mitochondria, it is probable that all extant
mitochondria can trace their origin to that singular primordial event at the dawn of eukaryotes. Yet, the evolution
has led to tremendous variety of mitochondria, their genomes, their regulation, and their functions, which are as
diverse as the organisms they reside in We are interested in understanding mitochondrial functions in malaria
parasites, pathogens that extract a tremendous toll from the health and wellbeing of vast multitudes. Over 30
years ago, our group discovered the unusual mtDNA in Plasmodium that encoded just 3 mitochondrial electron
transport chain (mtETC) subunits and ribosomal RNA in fragmented and scrambled pieces. With the long-term
support of this grant award, we have elucidated many aspects of mitochondrial functions in malaria parasites,
showing the organelle to be the target for antimalarial drugs currently in use as well as those in development.
We have shown which of the canonical mitochondrial functions are critical in blood stages and which are
essential only for the insect stages of the parasite. We have also identified unique and essential features of
Plasmodium mitochondrion using genetic and proteomic investigations. In recent years, our efforts have been
joined by other investigators working to understand the mitochondrion in apicomplexan parasites. Together, we
are at a stage when many of the mysteries surrounding this organelle in Plasmodium and Toxoplasma are being
addressed with the application of powerful new approaches. For the next funding period, we are proposing to
conduct studies that would bring us closer to answering some of the most critical questions remaining about
mitochondrial functions in malaria parasites. These include potential dual function of Complex III, understanding
the nature of mitochondrial complexes, and the unusual structural features of mitochondria in asexual and sexual
stages of the parasite. As before, the work we are proposing will be carried out by an outstanding collaborative
team including a consortium arrangement. Specifically, we will investigate an essential mitochondrial protein an
human orthologue of which has been shown to have multiple functions in mitochondrial biogenesis and
metabolism. These studies will use biochemical and metabolomic approaches in addition to genetic
manipulations. In a consortium arrangement, we will use cryo-electron tomography to study in situ unusual
features of mitochondrial structures in asexual and sexual stages of P. falciparum as well as consequences of
genetic disruptions of a select number of mitochondri...

## Key facts

- **NIH application ID:** 10803579
- **Project number:** 2R01AI028398-32A1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** AKHIL B VAIDYA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $625,728
- **Award type:** 2
- **Project period:** 1989-07-01 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803579

## Citation

> US National Institutes of Health, RePORTER application 10803579, Mitochondrial Functions in Malaria Parasites (2R01AI028398-32A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10803579. Licensed CC0.

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