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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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Autores principales: Rausser, Shannon, Trumpff, Caroline, McGill, Marlon A, Junker, Alex, Wang, Wei, Ho, Siu-Hong, Mitchell, Anika, Karan, Kalpita R, Monk, Catherine, Segerstrom, Suzanne C, Reed, Rebecca G, Picard, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612706/
https://www.ncbi.nlm.nih.gov/pubmed/34698636
http://dx.doi.org/10.7554/eLife.70899
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author Rausser, Shannon
Trumpff, Caroline
McGill, Marlon A
Junker, Alex
Wang, Wei
Ho, Siu-Hong
Mitchell, Anika
Karan, Kalpita R
Monk, Catherine
Segerstrom, Suzanne C
Reed, Rebecca G
Picard, Martin
author_facet Rausser, Shannon
Trumpff, Caroline
McGill, Marlon A
Junker, Alex
Wang, Wei
Ho, Siu-Hong
Mitchell, Anika
Karan, Kalpita R
Monk, Catherine
Segerstrom, Suzanne C
Reed, Rebecca G
Picard, Martin
author_sort Rausser, Shannon
collection PubMed
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 pubmed-86127062021-11-26 Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures Rausser, Shannon Trumpff, Caroline McGill, Marlon A Junker, Alex Wang, Wei Ho, Siu-Hong Mitchell, Anika Karan, Kalpita R Monk, Catherine Segerstrom, Suzanne C Reed, Rebecca G Picard, Martin eLife Cell Biology 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. eLife Sciences Publications, Ltd 2021-10-26 /pmc/articles/PMC8612706/ /pubmed/34698636 http://dx.doi.org/10.7554/eLife.70899 Text en © 2021, Rausser et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Rausser, Shannon
Trumpff, Caroline
McGill, Marlon A
Junker, Alex
Wang, Wei
Ho, Siu-Hong
Mitchell, Anika
Karan, Kalpita R
Monk, Catherine
Segerstrom, Suzanne C
Reed, Rebecca G
Picard, Martin
Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures
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 Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612706/
https://www.ncbi.nlm.nih.gov/pubmed/34698636
http://dx.doi.org/10.7554/eLife.70899
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