# Regulation of mitochondrial morphodynamics in Toxoplasma gondii

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $149,294

## Abstract

A unique feature of parasites of the phylum Apicomplexa, such as Toxoplasma gondii, is the presence of a
single tubular mitochondrion, which is essential for parasite survival and a validated drug target. Most studies
of the apicomplexan mitochondrion have focused on its biochemistry and physiology. By contrast little is known
about the machinery that controls mitochondrial division and that regulate its structure, information that would
be critical for a thorough exploration of the mitochondrion as a drug target. Toxoplasma's singular
mitochondrion is very dynamic and undergoes morphological changes throughout the parasite's life cycle
including during the transition from the intracellular to the extracellular environment. While inside a host cell the
mitochondrion is maintained in a lasso shape that stretches around the parasite periphery where it has regions
of coupling with the parasite pellicle, suggesting the presence of membrane contact sites. Promptly after exit
from the host cell, these contact sites disappear, and the mitochondrion collapses indicating that dynamic
membrane contact sites regulate the positioning of the mitochondrion. Neither the functional significance nor
the proteins needed for the contact between Toxoplasma's mitochondrion and pellicle are known. We have
discovered a novel protein, Fip1, that associates with the mitochondrion and that when knocked out the normal
morphology of the mitochondrion is severely affected. In intracellular fip1 knockout parasites the mitochondrion
is not in a lasso shape as seen in wildtype parasites, but instead it is collapsed. Additionally, proper
mitochondrial segregation is disrupted in the knockout parasites, resulting in parasites with no mitochondrion
and mitochondrial material outside of the parasites. These gross morphological changes are associated with a
significant reduction of parasite propagation and can be rescued by reintroduction of a wildtype copy of Fip1.
Accordingly, we hypothesize that Fip1 mediates contact between the mitochondrion and the parasite pellicle in
a regulatable fashion, and that the Fip1 dependent mitochondrial morphology and dynamics are critical for
parasite propagation. Through a combination of molecular genetics, microscopy and proteomics we will
address the functional relevance and the mechanics of the mitochondrial morphology. In aim one we will
conduct a thorough in vivo and in vitro phenotypic characterization of Fip1 mutant strains to determine the role
of Fip1 and mitochondrial shape in parasite viability. Aim two focuses on identifying and characterizing
components of the Fip1 complex that mediates the association of the mitochondrion with the periphery of the
parasites. Finally, in aim three we will determine the regulatory mechanisms that drive the mitochondrial
morphological changes as the parasite exits its host cell. In conjunction, these experiments will shed light onto
the molecular mechanisms driving and regulating the morphodynamics of ...

## Key facts

- **NIH application ID:** 11225243
- **Project number:** 7R01AI149766-06
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Gustavo A Arrizabalaga
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $149,294
- **Award type:** 7
- **Project period:** 2020-03-03 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11225243

## Citation

> US National Institutes of Health, RePORTER application 11225243, Regulation of mitochondrial morphodynamics in Toxoplasma gondii (7R01AI149766-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11225243. Licensed CC0.

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