Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
- Columbia University Irving Medical Center, United States
- University of Kentucky, United States
- University of Pittsburgh, United States
Abstract
Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly-defined immune cell subtypes, we quantify the natural variation in citrate synthase, mitochondrial DNA copy number (mtDNAcn), and respiratory chain enzymatic activities in human neutrophils, monocytes, B cells, and naïve and memory T lymphocyte subtypes. In mixed peripheral blood mononuclear cells (PBMCs) from the same individuals, we show to what extent mitochondrial measures are confounded by both cell type distributions and contaminating platelets. Cell subtype-specific measures among women and men spanning 4 decades of life indicate potential age- and sex-related differences, including an age-related elevation in mtDNAcn, which are masked or blunted in mixed PBMCs. Finally, a proof-of-concept, repeated-measures study in a single individual validates cell type differences and also reveals week-to-week changes in mitochondrial activities. Larger studies are required to validate and mechanistically extend these findings. These mitochondrial phenotyping data build upon established immunometabolic differences among leukocyte sub-populations, and provide foundational quantitative knowledge to develop interpretable blood-based assays of mitochondrial health.
Data availability
All data generated and analyzed during this study, including mitochondrial biochemistry, mtDNA content, and blood chemistry, cell counts from CBC and flow cytometry, and de-identified participant information are included in the supporting data files. Source data files have been provided for Figures 1-9, and for figure supplements (Figure 1-figure supplement 3, Figure 2-figure supplement 1, Figure 4-figure supplement 1, Figure 4-figure supplement 2, Figure 6-figure supplement 1, Figure 6-figure supplement 2, Figure 6-figure supplement 3, and Supplementary file 3). Requests for resources or other information should be directed to and will be fulfilled by the corresponding author.
Article and author information
Author details
Funding
Nathaniel Wharton Fund
- Martin Picard
National Institutes of Health (MH119336,GM119793,MH122706,AG066828,AG056635,AG026307,UL1TR001873)
- Martin Picard
National Institutes of Health (P30CA013696)
- Wei Wang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Simon C Johnson, University of Washington, United States
Ethics
Human subjects: The study was approved by New York State Psychiatric Institute (Protocol #7618) and all participants provided written informed consent for the study procedures and reporting of results.
Version history
- Preprint posted: October 16, 2020 (view preprint)
- Received: June 2, 2021
- Accepted: October 26, 2021
- Accepted Manuscript published: October 26, 2021 (version 1)
- Version of Record published: November 24, 2021 (version 2)
Copyright
© 2021, Rausser et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
eLife 10:e70899.
https://doi.org/10.7554/eLife.70899
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