RT Journal Article
SR Electronic
T1 Mitochondrial profiling reveals dynamic, sex- and age-specific mitochondrial phenotypes in human immune cell subtypes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.16.342923
DO 10.1101/2020.10.16.342923
A1 Shannon Rausser
A1 Caroline Trumpff
A1 Marlon A McGill
A1 Alex Junker
A1 Wei Wang
A1 Siu-hong Ho
A1 Anika Mitchell
A1 Kalpita R Karan
A1 Catherine Monk
A1 Suzanne C. Segerstrom
A1 Rebecca G. Reed
A1 Martin Picard
YR 2020
UL http://biorxiv.org/content/early/2020/10/16/2020.10.16.342923.abstract
AB How mitochondria functionally differ between immune cell subtypes, between the sexes, across ages, and whether they dynamically change over time has not been characterized. Here we deploy a high-throughput mitochondrial phenotyping platform to define cell-type specific mitochondrial features in circulating immune cell subtypes. In women and men spanning four decades of life, we find that mitochondrial content, mitochondrial DNA copy number (mtDNAcn), and respiratory chain enzymatic activities vary by up to 3.5-fold between neutrophils, monocytes, B and T lymphocyte subtypes. Within individuals, mitochondrial content and mtDNAcn, and to a lesser degree respiratory chain function, are strongly correlated with each other across immune cell types, suggesting their systemic harmonization. Moreover, repeated weekly measurements of mitochondrial features in the same individual reveal remarkable variation in mitochondrial content and respiratory chain function over time. This suggests that immune cell mitochondria exhibit dynamic state properties, which we find to be partially correlated with circulating biomarkers. We also define multivariate mitochondrial phenotypes – mitotypes – that distinguish lymphoid from myeloid cell types, naïve-to-memory lymphocyte states, and moderately differ between women and men. Finally, we compare mitochondrial features of purified cell subtypes to peripheral blood mononuclear cells (PBMCs) and determine the influence of contaminating platelets and of variable cell type composition. Our results invite caution in using cell type mixtures to infer person-level mitochondrial behavior. Together, these findings identify dynamic cell-type specific variation in mitochondrial biology among circulating leukocytes and provide foundational knowledge to develop interpretable blood-based assays of mitochondrial health.Competing Interest StatementThe authors have declared no competing interest.