# ELMOD2: proposed roles in regulating mitochondrial fusion and cell cycle

> **NIH NIH F31** · EMORY UNIVERSITY · 2021 · $46,036

## Abstract

PROJECT SUMMARY
 Cancers, though heterogeneous in pathology, are a product of unchecked cell growth caused by perturbation
to essential cellular processes, notably energy metabolism, DNA replication, or the cell cycle. Misregulation of
these pathways can cause severe phenotypes that, together, can lead to oncogenesis: increased DNA content,
multinucleation, supernumerary centrosomes, and increased dependence upon glycolysis as the cellular source
of ATP (resulting in changes to mitochondrial morphology, gene expression, and functions). Even though these
cancer hallmarks have been intensively studied, the mechanism by which lesions to these pathways promote
oncogenesis remains unclear in most cases.
 My lab studies ARF family GTPases and the mechanisms that they employ to regulate a wide variety of
essential cellular activities that, when perturbed, can lead to severe pathologies. I used CRISPR technologies to
generate cell lines lacking expression of ELMOD2, a regulator of several members of the ARF family. I
discovered that ELMOD2-/- lines have fragmented mitochondria, and they also have increases in mitotic indices,
supernumerary centrosomes, increased DNA content, multinucleation, and multiciliation, consistent with a defect
in the cell cycle. Thus, I hypothesize that ELMOD2 both acts from inside mitochondria to mediate effects of the
ARL2 GTPase on mitochondrial fusion as well as regulates cytokinesis from a distinct cellular compartment. To
tease apart the underlying mechanisms that drive these functions, I will use mammalian cell culture to visualize
and assess mitochondrial activity and cell cycle. In Aim 1, I will determine if ELMOD2 acts downstream of ARL2
to regulate mitochondrial fusion, independent of its roles in cell cycle. I will perform a series of rescue experiments
to characterize ELMOD2’s role in this pathway and its relationship to other players in mitochondrial fusion. In
Aim 2, I will define ELMOD2’s functions in cell cycle. I will begin by teasing apart the stage of cell cycle that is
perturbed by loss of ELMOD2. I will determine which ARF family GTPase(s) ELMOD2 works with to alter
mitochondrial dynamics and cell cycle. Overall, this project will contribute to our fundamental understanding of
mitochondrial fusion and cell cycle, two critical pathways whose regulation is incompletely understood. This will
broaden our understanding of regulatory GTPase biology and how GAPs may facilitate multi-pathway
communication. Such findings will pave the way for the future design of novel therapeutics that will precisely
target the source of cancer and other pathologies.

## Key facts

- **NIH application ID:** 10070591
- **Project number:** 5F31CA236493-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rachel Elizabeth Turn
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2018-12-17 → 2023-03-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070591

## Citation

> US National Institutes of Health, RePORTER application 10070591, ELMOD2: proposed roles in regulating mitochondrial fusion and cell cycle (5F31CA236493-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10070591. Licensed CC0.

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