Journal Article Research Support, N.I.H., Extramural Ppublish
PubMed: 42144122 DOI: 10.1016/j.mito.2026.102169
Electron microscopy visualization of cell-free mitochondrial DNA-associated vesicular structures in human plasma, serum, and saliva.
Mitochondrion 91:102169
Authors: Alexandra Volos, Soah Grace Franklin, Jeremy Michelson, Shannon Rausser, Jonathan R Brestoff, Martin Picard
Affiliations
- Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, NY 10032, United States.
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
- Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, NY 10032, United States; Department of Neurology, H. Houston Merritt Center for Neurological and Mitochondrial Disorders, Columbia University Irving Medical Center, New York, New York 10032, United States; New York State Psychiatric Institute, New York, NY 10032, United States; Robert N Butler Columbia Aging Center, Mailman School of Public Health, New York, NY 10032, United States.
Abstract
Human biofluids contain cell-free mitochondrial DNA (cf-mtDNA) and extracellular mitochondria (ex-Mito), creating the challenge of defining their origins, destinations, mechanisms of regulation, and biological purpose(s). To expand our understanding of vesicular structures across human biofluids, we present a descriptive electron microscopy analysis of circulating particles from cf-mtDNA-enriched plasma (citrate, heparin, and EDTA), serum (red and gold top), and saliva collected from ten healthy participants (5 females, 5 males, mean age 44.9 years). Ex-mito and extracellular vesicles (EVs) were isolated by centrifugation followed by size-exclusion chromatography, imaged by transmission electron microscopy, and morphometrically analyzed. In parallel, cf-mtDNA was quantified in each biofluid to confirm enrichment. The resulting catalog of the most common circulating particles in plasma, serum, and saliva show that circulating double-membrane extracellular particles are present across human biofluids, along with EVs and other particle types. Combining imaging with cf-mtDNA quantification, we show that individuals with higher plasma cf-mtDNA concentrations tend to contain more double-membrane, ex-Mito-like particles. These preliminary and largely qualitative results do not directly demonstrate but are consistent with the concept of mitochondria transfer and/or signaling between cells and tissues. The image inventory provided here expands our knowledge of cell-free mitochondrial biology and provides a resource to inform biofluid selection and technical considerations in future studies quantifying ex-Mito and cf-mtDNA.
MeSH
Cells, Serum, Mitochondria, Microscopy, Electron, Microscopy, Dna, Mitochondrial, Dna, Membranes, Plasma