Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures

Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly defined immune cell subtypes, we quantify the natural variation in mitochondrial DNA copy number (mtDNAcn), citrate synthase, and respiratory chain enzymatic activities in human n...

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Main Authors: Shannon Rausser, Caroline Trumpff, Marlon A McGill, Alex Junker, Wei Wang, Siu-Hong Ho, Anika Mitchell, Kalpita R Karan, Catherine Monk, Suzanne C Segerstrom, Rebecca G Reed, Martin Picard
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-10-01
Series:eLife
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Online Access:https://elifesciences.org/articles/70899
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author Shannon Rausser
Caroline Trumpff
Marlon A McGill
Alex Junker
Wei Wang
Siu-Hong Ho
Anika Mitchell
Kalpita R Karan
Catherine Monk
Suzanne C Segerstrom
Rebecca G Reed
Martin Picard
author_facet Shannon Rausser
Caroline Trumpff
Marlon A McGill
Alex Junker
Wei Wang
Siu-Hong Ho
Anika Mitchell
Kalpita R Karan
Catherine Monk
Suzanne C Segerstrom
Rebecca G Reed
Martin Picard
author_sort Shannon Rausser
collection DOAJ
description Using a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly defined immune cell subtypes, we quantify the natural variation in mitochondrial DNA copy number (mtDNAcn), citrate synthase, 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 four 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 subpopulations, and provide foundational quantitative knowledge to develop interpretable blood-based assays of mitochondrial health.
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spelling doaj.art-66750d7ee5894ea68f42b14e43507f682022-12-22T03:52:26ZengeLife Sciences Publications LtdeLife2050-084X2021-10-011010.7554/eLife.70899Mitochondrial phenotypes in purified human immune cell subtypes and cell mixturesShannon Rausser0https://orcid.org/0000-0003-0425-1571Caroline Trumpff1Marlon A McGill2Alex Junker3Wei Wang4https://orcid.org/0000-0001-9890-2122Siu-Hong Ho5Anika Mitchell6Kalpita R Karan7Catherine Monk8Suzanne C Segerstrom9Rebecca G Reed10Martin Picard11https://orcid.org/0000-0003-2835-0478Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United StatesDepartment of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United StatesDepartment of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United StatesDepartment of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United StatesColumbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, United StatesColumbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, United StatesDepartment of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United StatesDepartment of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United StatesDepartment of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States; Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, United States; New York State Psychiatric Institute, New York, United StatesDepartment of Psychology, University of Kentucky, Lexington, United StatesDepartment of Psychology, University of Pittsburgh, Pittsburgh, United StatesDepartment of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States; New York State Psychiatric Institute, New York, United States; Department of Neurology, Merritt Center and Columbia Translational Neuroscience Initiative, Columbia University Irving Medical Center, New York, United StatesUsing a high-throughput mitochondrial phenotyping platform to quantify multiple mitochondrial features among molecularly defined immune cell subtypes, we quantify the natural variation in mitochondrial DNA copy number (mtDNAcn), citrate synthase, 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 four 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 subpopulations, and provide foundational quantitative knowledge to develop interpretable blood-based assays of mitochondrial health.https://elifesciences.org/articles/70899mitochondrialeukocytessexual dimorphismagingdynamic variationimmunometabolism
spellingShingle Shannon Rausser
Caroline Trumpff
Marlon A McGill
Alex Junker
Wei Wang
Siu-Hong Ho
Anika Mitchell
Kalpita R Karan
Catherine Monk
Suzanne C Segerstrom
Rebecca G Reed
Martin Picard
Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
eLife
mitochondria
leukocytes
sexual dimorphism
aging
dynamic variation
immunometabolism
title Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
title_full Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
title_fullStr Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
title_full_unstemmed Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
title_short Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
title_sort mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
topic mitochondria
leukocytes
sexual dimorphism
aging
dynamic variation
immunometabolism
url https://elifesciences.org/articles/70899
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