ArticlePsychoneuroendocrinology2022
Dynamic behavior of cell-free mitochondrial DNA in human saliva.
Article in Psychoneuroendocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Role of microRNA in the risk stratification of ischemic strokes.Frontiers in neurology · 2025Pooled it
- Article
- Saliva cell-free mitochondrial DNA (cf-mtDNA) response during physical and cognitive stress.medRxiv : the preprint server for health sciences · 2026Article
- Blood and urine cell-free circulating DNA in older adults with sarcopenia: a hypothesis-generating study.European geriatric medicine · 2026Article
- Saliva cell-free mitochondrial DNA (cf-mtDNA) as a dynamic biomarker of stress and emotion in daily life: Evidence from two independent repeated-measures studies.medRxiv : the preprint server for health sciences · 2026Article
- Examining saliva proteomic dynamics in mitochondrial diseases from a perspective of intrinsic health.Scientific reports · 2025Article
- Diurnal dynamics and psychobiological regulation of cell-free mitochondrial and nuclear DNA in human saliva.medRxiv : the preprint server for health sciences · 2025Article
- Salivary mitochondrial DNA is associated with biomarkers of Alzheimer's disease in cognitively normal older adults.Translational psychiatry · 2025Article
- Saliva and blood cell-free mtDNA reactivity to acute psychosocial stress.Psychoneuroendocrinology · 2025Article
- The energetic stress cytokine GDF15 is elevated in the context of chronic and acute psychosocial stress.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders.Journal of neuroinflammation · 2025Review
- Cell-free DNA release following psychosocial and physical stress in women and men.Translational psychiatry · 2025Article
- The researcher's guide to selecting biomarkers in mental health studies.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Review
- Pre-Analytical Factors Affecting Extracellular DNA in Saliva.Diagnostics (Basel, Switzerland) · 2024Article
- Saliva, a molecular reflection of the human body? Implications for diagnosis and treatment.Cell stress · 2024Article
- The Diagnostic, Prognostic, and Therapeutic Potential of Cell-Free DNA with a Special Focus on COVID-19 and Other Viral Infections.International journal of molecular sciences · 2023Review
- MitoQuicLy: A high-throughput method for quantifying cell-free DNA from human plasma, serum, and saliva.Mitochondrion · 2023Article
- MitoQuicLy: a high-throughput method for quantifying cell-free DNA from human plasma, serum, and saliva.bioRxiv : the preprint server for biology · 2023Article
- Isolation of salivary cell-free DNA for cancer detection.PloS one · 2023Article
- Mitochondrial DNA copy number in autism spectrum disorder and attention deficit hyperactivity disorder: a systematic review and meta-analysis.Frontiers in psychiatry · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Mitochondria contain their own genome that can be released in multiple biofluids such as blood and cerebrospinal fluid, as cell-free mitochondrial DNA (cf-mtDNA). In clinical studies, blood cf-mtDNA predicts mortality and higher cf-mtDNA levels are associated with mental and physical stress. However, the dynamics of cf-mtDNA has not been defined, and whether it can be measured non-invasively like other neuroendocrine markers in saliva has not been examined. Here we report cf-mtDNA in human saliva and establish its natural within-person dynamic behavior across multiple weeks. In a small proof-of-principle cohort of healthy adults, we first develop an approach to rapidly quantify salivary cf-mtDNA without DNA isolation, and demonstrate the existence of salivary cf-mtDNA. We then deploy this approach to perform an intensive repeated-measures analysis of two healthy men studied at 4 daily timepoints over 53-60 consecutive days (n = 212-220 observations each) with parallel measures of steroid hormones, self-reported daily mood, and health-related behaviors. Salivary cf-mtDNA exhibited a robust awakening response reaching up to two orders of magnitude 30-45 min after awakening, varied from day-to-day, and moderately correlated with the cortisol awakening response. In exploratory analyses, no consistent association with self-reported daily mood/health-related behaviors were found, although this requires further examination in future studies. Dynamic variation in cf-mtDNA was inversely related with salivary interleukin 6 (IL-6), inconsistent with a pro-inflammatory effect of salivary cf-mtDNA. The highly dynamic behavior of salivary cf-mtDNA opens the door to non-invasive studies examining the relevance of mtDNA signaling in relation to human health.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.