# Investigating the Molecular Mechanisms of Mitochondrial Calcium Uptake in Caenorhabditis elegans

> **NIH NIH R21** · ALBANY MEDICAL COLLEGE · 2022 · $244,499

## Abstract

PROJECT SUMMARY
The enormous societal burden caused by neurodegenerative disorders, stresses the importance of
determining the underlying pathological mechanisms that promote disease. Both deregulated calcium signaling
and disrupted mitochondrial function are a common symptom observed in neurodegenerative disorders,
including amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. However, the underlying
role these defects have in mediating pathology and if they impact each other to promote disease is not fully
understood. In addition to their role in energy production, mitochondria function to sequester large influxes of
cytosolic calcium and act as an organellular calcium buffer. However, the influx of calcium into the
mitochondrial also stimulates the activity of the mitochondria, such as the tricarboxylic acid cycle, oxidative
phosphorylation, the production of reactive oxygen species, and it can also trigger cell death. The
phylogenetically conserved mitochondrial calcium uniporter complex mediates the uptake of calcium into the
mitochondria. With the recent molecular identification of mitochondrial calcium uniporter complex components,
many current studies have implicated altered mitochondrial calcium homeostasis as having a fundamental role
in promoting neurodegeneration. These data highlight the importance of understanding the mechanisms that
mediate mitochondrial calcium homeostasis. Here, we propose to utilize the genetic amenability and simplicity
of C. elegans to 1) interrogate the role of the four core components of the mitochondrial calcium uniporter
complex in an in vivo model system to establish a foundation of mitochondrial calcium uniporter complex
function and to 2) discover new gene products that are involved in mitochondrial calcium influx. From these
studies, our goals are to improve our understanding of mitochondrial calcium uptake and homeostasis and to
provide critical guidance for the development of novel therapeutic strategies for treating neurodegenerative
diseases.

## Key facts

- **NIH application ID:** 10456980
- **Project number:** 5R21AG073893-02
- **Recipient organization:** ALBANY MEDICAL COLLEGE
- **Principal Investigator:** Kenneth R Norman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $244,499
- **Award type:** 5
- **Project period:** 2021-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456980

## Citation

> US National Institutes of Health, RePORTER application 10456980, Investigating the Molecular Mechanisms of Mitochondrial Calcium Uptake in Caenorhabditis elegans (5R21AG073893-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10456980. Licensed CC0.

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