# Melatonin biosynthesis in neuronal mitochondria

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $386,046

## Abstract

Melatonin is a neuroprotective hormone with pleiotropic properties, many of which are modulated by the
mitochondria. Melatonin is found in neuronal mitochondria. However, little is known about the synthesis or
transport of melatonin in neurons. Our preliminary data suggest that melatonin is produced in neuronal
mitochondria and the hypothesis of this project is that neuronal melatonin is synthesized in the mitochondrial
matrix; that AANAT activity (the rate limiting enzyme in the melatonin synthesis pathway) in the mitochondria is
regulated by phosphorylation and interaction with the 14-3-3 chaperone, and that melatonin synthesized in the
mitochondria remains in the neuron where it acts locally to protect neurons from cellular stress. To test this
hypothesis, we will propose a research design that will accomplish three Aims. Aim 1 will characterize the
mitochondrial melatonin synthesis pathway, including localizing each of the four melatonin synthesis enzymes
and determining how they are transported to subcellular membrane and organelles. In Aim 2 we will determine
the mechanisms responsible for regulating melatonin synthesis in neurons. Aim 3 will focus on the intracellular
transport of mitochondrially-produced melatonin. The data generated from this project will provide a novel
foundation for understanding the protective action of melatonin on neurons and opens a new research avenue
for mitochondrial melatonin pharmacology and biology.

## Key facts

- **NIH application ID:** 10145805
- **Project number:** 5R01NS100743-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Robert M. Friedlander
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $386,046
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145805

## Citation

> US National Institutes of Health, RePORTER application 10145805, Melatonin biosynthesis in neuronal mitochondria (5R01NS100743-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145805. Licensed CC0.

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