# Molecular Regulations of Mitochondrial Structure in Neuronal Homeostasis and Survival

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $381,695

## Abstract

Mitochondrial malfunction is well known to manifest as dysfunction of neurons, due to the high
energetic demands of these highly polarized cells, their remarkable axonal length, and complexity.
However, how neuronal mitochondria precisely control crista structure in response to ever-
changing energy demands and oxidative stressors and how these regulations impact neuronal
function and behavior in multicellular organisms remain elusive. In our Preliminary Studies, we
have discovered an evolutionarily conserved role for MIC60 in maintaining crista structure in
Drosophila. We have found molecular modifications of fly MIC60 (dMIC60) including
phosphorylation and oxidation and their significance in maintaining crista junction plasticity and
resisting oxidative stress. These results demonstrate the vital importance of dMIC60 and its
posttranslational modifications for mitochondrial and neuronal homeostasis. We hypothesize that
molecular regulations of dMIC60 including phosphorylation and oxidation allow dMIC60 to receive
cellular signals to conduct its functions and that their misregulations could lead to neuronal
dysfunction and degeneration. To test this hypothesis, we will perform the following Specific Aims.
Aim 1: Roles for dMIC60 in neuronal homeostasis. Aim 2: Crista structure as a cellular
cause for oxidative damage. Aim 3: Molecular mechanisms of dMIC60 phosphorylation and
oxidation.

## Key facts

- **NIH application ID:** 10833197
- **Project number:** 5R01NS128040-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** XINNAN WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $381,695
- **Award type:** 5
- **Project period:** 2022-07-20 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833197

## Citation

> US National Institutes of Health, RePORTER application 10833197, Molecular Regulations of Mitochondrial Structure in Neuronal Homeostasis and Survival (5R01NS128040-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10833197. Licensed CC0.

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