# Mitochondrial Interactions with the Plasmamembrane: Genetic Underpinnings and Functional Consequences at Drosophila Nerve Terminals.

> **NIH NIH R01** · FLORIDA ATLANTIC UNIVERSITY · 2021 · $365,192

## Abstract

ABSTRACT
Our overall goal is to elucidate the different mechanisms available to a neuron to control mitochondria
at a subcellular level, and the genetic bases of these capabilities. Mitochondria accumulate within nerve
terminals where they generate most of the ATP required to package and recycle neurotransmitters and
to maintain transmembrane ion-balances. Neural function is reliant on mitochondrial function to sustain
neurotransmitter release, and mitochondrial dysfunction is a hallmark of many neurodegenerative
diseases. It is therefore imperative to gain a better understanding of the mechanisms that neurons use
to control mitochondria at the sub-cellular level of nerve terminals, and how this might differ between
neuron types. Here we present the hypothesis that sites at which mitochondria interact with the plasma
membrane (PM) represent a form of mitochondrial utilization that confers advantages in those parts of a
neuron with high power demands, such as nerve terminals. We propose to elucidate the functional
significance of such interactions, and their genetic underpinnings. To do this we are adopting a
structure-function approach, exploiting the small size and genetic tools of Drosophila. In Aim 1 we will
use serial block face scanning electron microscopy to determine the neuron types, and subcellular
regions served by mitochondrial-PM interactions. In Aim 2 we will use a novel form of super-resolution
to investigate the formation and disassembly of these interactions, and the functional consequences for
presynaptic physiology and neurotransmission. In Aim 3 we will investigate the role of a select group of
genes identified as candidates for a role in mitochondrial-PM interactions. The significance of this
proposal lies in its potential to uncover novel neuronal and sub-cellular specific mitochondrial functions,
and the genetic bases of these functions, which may throw light on the selective neuronal vulnerability
observed in different neurodegenerative diseases and neurological conditions.

## Key facts

- **NIH application ID:** 10279265
- **Project number:** 1R01NS123377-01
- **Recipient organization:** FLORIDA ATLANTIC UNIVERSITY
- **Principal Investigator:** GREGORY TALISKER MACLEOD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $365,192
- **Award type:** 1
- **Project period:** 2021-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10279265

## Citation

> US National Institutes of Health, RePORTER application 10279265, Mitochondrial Interactions with the Plasmamembrane: Genetic Underpinnings and Functional Consequences at Drosophila Nerve Terminals. (1R01NS123377-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10279265. Licensed CC0.

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