# Psychobiological Regulation of Cell-Free Mitochondrial DNA in Human Saliva

> **NIH NIH R21** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $283,500

## Abstract

PROJECT SUMMARY
Mitochondria are an emerging signaling organelle involved in stress regulation and mental health. Identifying
mechanisms of mitochondrial signaling, including secreted molecules and their dynamic regulation, will provide
the necessary tools to elucidate their role in stress pathophysiology and other disease conditions. We and others
have recently established that mitochondria can release their own genome as cell-free mitochondrial DNA (cf-
mtDNA), a potentially immunogenic molecule present in varying levels in human blood, particularly under
conditions of psychological stress and psychopathology. Building on our recent discovery that cf-mtDNA is
detectable in human saliva, we now propose foundational studies necessary to establish saliva cf-mtDNA as a
useful marker for human research. Based on our preliminary studies, this 2-year R21 proposal aims to i) map
the natural awakening response and diurnal variation of cf-mtDNA in healthy adult premenopausal women and
in men; ii) define the association between cf-mtDNA and key steroid hormones with already well-defined diurnal
rhythms, including cortisol; iii) leveraging already-collected saliva samples from a stress induction protocol,
establish whether saliva cf-mtDNA is inducible by acute socioevaluative stress; and iv) whether saliva cf-mtDNA
mirrors blood levels or whether cf-mtDNA is independently regulated in these two different biofluids. Together,
these studies will establish potential sex differences in saliva cf-mtDNA dynamic across time scales, and provide
the necessary basis to establish cf-mtDNA as a marker of mitochondrial stress in both mechanistic and
epidemiological studies.

## Key facts

- **NIH application ID:** 10218618
- **Project number:** 1R21MH123927-01A1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Martin Picard
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $283,500
- **Award type:** 1
- **Project period:** 2021-07-22 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218618

## Citation

> US National Institutes of Health, RePORTER application 10218618, Psychobiological Regulation of Cell-Free Mitochondrial DNA in Human Saliva (1R21MH123927-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10218618. Licensed CC0.

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