Abstract
How mitochondria functionally differ between immune cell subtypes, between the sexes, and with aging has not been defined in humans. We deploy a high-throughput mitochondrial phenotyping platform to define cell-type specific mitochondrial features in human 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. Mitochondria exhibit specific age- and sex-related differences among individual cell subtypes, including an age-related increase in mtDNAcn. In an intensive repeated-measures study, we also identify remarkable weekly variation in mitochondrial content and respiratory chain function, which is partially correlated with changes in circulating biomarkers. Our results 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, a comparison of mitochondrial features in purified cell subtypes and in peripheral blood mononuclear cells (PBMCs) invites caution in using cell type mixtures to infer person-level mitochondrial function. 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 Statement
The authors have declared no competing interest.