# Persistent Mitochondrial and Epigenetic Effects of Early Life Toxicant Exposure

> **NIH NIH P42** · DUKE UNIVERSITY · 2021 · $259,225

## Abstract

Duke University's Superfund Research Center examines the problem of early life exposure to hazardous
chemicals and later life consequences. Growing evidence suggests that the toxic effects of certain chemicals
on mitochondrial function can be highly persistent, and that some individuals may be more sensitive due to
genetic differences. Mitochondria undergo biogenesis and major functional changes during early development
and cellular differentiation, periods during which epigenetic reprogramming also occurs. We will test the
hypotheses that mitochondrial toxicity during vulnerable, plastic windows of mitochondrial and
epigenetic programming results in persistent mitochondrial dysfunction, persistent epigenetic
repatterning, and that these changes are mechanistically linked. We will assess the persistence of both
mitochondrial and epigenetic changes throughout life, and through three subsequent generations, to test the
possibility that effects are persistent even in the absence of direct chemical exposure. We acknowledge and
will also test the possibilities that persistent mitochondrial effects are not mediated by epigenetic changes, and
that epigenetic changes may occur but not have effects on mitochondrial function. Finally, we will also test the
hypothesis that mitochondrial dysfunction will be exacerbated in genetic backgrounds, chosen on the basis of
human mitochondrial disease relevance, in which mitochondrial homeostatic processes are reduced.
Innovative aspects of this proposal include: 1) examination of epigenetic and transcriptional changes linked to
mitochondrial disruption during potentially sensitive windows of time early in development and during cellular
differentiation; 2) analysis of less-studied histone modifications in conjunction with better-studied cytosine
methylation; 3) systematic examination of the effects of deficiencies in genetic pathways that modulate
mitochondrial toxicity; and 4) development of high-throughput, rapid, in vivo and in vitro systems for testing
persistent and trasngenerational effects.

## Key facts

- **NIH application ID:** 10144454
- **Project number:** 5P42ES010356-19
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Joel Newman Meyer
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $259,225
- **Award type:** 5
- **Project period:** 2000-06-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144454

## Citation

> US National Institutes of Health, RePORTER application 10144454, Persistent Mitochondrial and Epigenetic Effects of Early Life Toxicant Exposure (5P42ES010356-19). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10144454. Licensed CC0.

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