Immune Cell Mitochondrial Phenotypes Are Largely Preserved in Mitochondrial Diseases and Do Not Reﬂect Disease Severity

Q: What was the study’s main goal regarding immune cells and mitochondria?

To profile immune cell mitochondrial phenotypes in mitochondrial diseases and assess how these phenotypes relate to disease manifestations or biomarkers.

Q: Which mitochondrial measurements were used in the analysis?

The study quantified mitochondrial content and oxidative phosphorylation (OxPhos) enzymatic activities, including complexes I, II, and IV, as well as mitochondrial respiratory capacity (MRC) index.

Q: How did mitochondrial phenotypes in immune cells relate to disease severity?

Across mitochondrial measures, differences between MitoD and controls were generally small, and immune cell mitochondrial phenotypes were generally unrelated to symptom severity.

Sep 28, 2026

Uploaded by Alexandar

This open-access research article profiles mitochondrial phenotypes in immune cells from individuals with mitochondrial diseases (MitoD) and evaluates links to disease manifestations and biomarkers. The study measures mitochondrial content and oxidative phosphorylation (OxPhos) enzyme activities in isolated monocytes, lymphocytes, neutrophils, platelets, and PBMCs from 37 MitoD individuals and 68 healthy controls. Findings show strong cell type differences, with MitoD-associated changes generally small and largely unrelated to symptom severity.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Background and Objectives

Methods

Results

Conclusions

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RESEARCH ARTICLE OPEN ACCESS Immune Cell Mitochondrial Phenotypes Are Largely Preserved in Mitochondrial Diseases and Do Not Reﬂect Disease Severity Cynthia C. Liu,1 Mangesh Kurade,1 Anna S. Monzel,1 Catherine Kelly,1 Robert-Paul Juster,2 Caroline Trumpff,1 Michio Hirano,3 and Martin Picard1,3,4,5 Correspondence Dr. Picard [mp3484@cumc.columbia.edu](mp3484@cumc.columbia.edu) Neurol Genet 2026;12:e200343 . doi:10 . 1212/NXG.0000000000200343 Abstract Background and Objectives The aim of this study was to proﬁle immune cell mitochondrial phenotypes in mitochondrial diseases (MitoD) and evaluate how these phenotypes relate to disease manifestations or biomarkers. Methods We proﬁled mitochondrial content and oxidative phosphorylation (OxPhos) enzymatic activities in isolated monocytes, lymphocytes, neutrophils, platelets, and mixed peripheral blood mononuclear cells (PBMCs) from 37 individuals with MitoD (m.3243A > G, n = 23; single, large-scale mitochondrial DNA (mtDNA) deletions, n = 14) and 68 healthy women and men from the Mitochondrial Stress, Brain Imaging, and Epigenetics study. Results We ﬁrst conﬁrmed and quantiﬁed robust cell type diﬀerences in mitochondrial content; activities ofOxPhos complexes I, II, and IV; and the mitochondrial respiratory capacity (MRC) index. In relation to MitoD, neither mitochondrial content nor OxPhos capacity was consistently aﬀected, other than a mild monocyte-speciﬁc reduction in complex I (partially mtDNA encoded) relative to complex II (entirely nDNA encoded), consistent with the mtDNA defects examined. Relative to the large diﬀerences in cell type–speciﬁc mitochondrial phenotypes, diﬀerences in MitoD relative to controls were generally small (<25%) across mitochondrial measures. MitoD biomarkers growth diﬀerentiation factor 15 and ﬁbroblast growth factor 21, as well as clinical disease severity measures, were most strongly related to mitochondrial abnormalities in platelets, and most weakly related to mitochondrial OxPhos capacity in lymphocytes, which are known to eliminate mtDNA defects. Finally, comparing PBMCs collected in the morning/fasted state with those in the afternoon/fed state after a stressful experience, wereport signiﬁcant time-dependent changes in mitochondrial biology over hours. Conclusions Overall, these results demonstrate that the dynamic and cell type–speciﬁc mitochondrial phenotypes are preserved in MitoD and are generally unrelated to symptom severity. Introduction There is growing interest in probing mitochondrial health proﬁles using blood-based bioenergetic measures.1-3 Mitochondrial oxidative phosphorylation (OxPhos) capacity deﬁcits and changes in blood immune cells have been identiﬁed in neurodegenerative diseases such as Alzheimer disease, metabolic diseases such as diabetes and sepsis, and psychiatric disorders MORE ONLINE Supplementary Material 1Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York; 2Department of Psychiatry and Addiction, University of Montreal, Quebec, Canada; 3Department of Neurology, H. Houston Merritt Center, Columbia Translational Neuroscience Initiative, Columbia University Medical Center, New York; 4New York State Psychiatric Institute, New York; and 5Robert N Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York. The Article Processing Charge was funded by the authors. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2026 The Author(s) . Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. e200343(1) Glossary BCA = bicinchoninic acid; CBC = complete blood count;

FAQs

What was the study’s main goal regarding immune cells and mitochondria?

To profile immune cell mitochondrial phenotypes in mitochondrial diseases and assess how these phenotypes relate to disease manifestations or biomarkers.

Which mitochondrial measurements were used in the analysis?

The study quantified mitochondrial content and oxidative phosphorylation (OxPhos) enzymatic activities, including complexes I, II, and IV, as well as mitochondrial respiratory capacity (MRC) index.

How did mitochondrial phenotypes in immune cells relate to disease severity?

Across mitochondrial measures, differences between MitoD and controls were generally small, and immune cell mitochondrial phenotypes were generally unrelated to symptom severity.

Sep 28, 2026

Uploaded by Alexandar