Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures

eLife

Siu-Hong Ho¹  Wei Wang¹  Shannon Rausser²  Kalpita R Karan²  Marlon A McGill²  Anika Mitchell²  Alex Junker²  Caroline Trumpff²  Catherine Monk³  Martin Picard⁴  Suzanne C Segerstrom⁵  Rebecca G Reed⁶ 

[1]Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, United States

[2]Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States

[3]Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States

[4]Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, United States

[5]New York State Psychiatric Institute, New York, United States

[6]Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, United States

[7]New York State Psychiatric Institute, New York, United States

[8]Department of Neurology, Merritt Center and Columbia Translational Neuroscience Initiative, Columbia University Irving Medical Center, New York, United States

[9]Department of Psychology, University of Kentucky, Lexington, United States

[10]Department of Psychology, University of Pittsburgh, Pittsburgh, United States

关键词: mitochondria;    leukocytes;    sexual dimorphism;    aging;    dynamic variation;    immunometabolism;    mitotypes;    Human;   

DOI  :  10.7554/eLife.70899

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY