Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients

Although impaired mitochondrial function has been proposed as a hallmark of multiple sclerosis (MS) disease, few studies focus on the mitochondria of immune cells. We aimed to compare the mitochondrial function of the peripheral blood mononuclear cells (PBMCs) from MS patients with (M+) and without...

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Main Authors: María Inmaculada Domínguez-Mozo, María Celeste García-Frontini Nieto, María Isabel Gómez-Calcerrada, Silvia Pérez-Pérez, María Ángel García-Martínez, Luisa María Villar, Noelia Villarrubia, Lucienne Costa-Frossard, Rafael Arroyo, Roberto Alvarez-Lafuente
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/11/11/1633
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author María Inmaculada Domínguez-Mozo
María Celeste García-Frontini Nieto
María Isabel Gómez-Calcerrada
Silvia Pérez-Pérez
María Ángel García-Martínez
Luisa María Villar
Noelia Villarrubia
Lucienne Costa-Frossard
Rafael Arroyo
Roberto Alvarez-Lafuente
author_facet María Inmaculada Domínguez-Mozo
María Celeste García-Frontini Nieto
María Isabel Gómez-Calcerrada
Silvia Pérez-Pérez
María Ángel García-Martínez
Luisa María Villar
Noelia Villarrubia
Lucienne Costa-Frossard
Rafael Arroyo
Roberto Alvarez-Lafuente
author_sort María Inmaculada Domínguez-Mozo
collection DOAJ
description Although impaired mitochondrial function has been proposed as a hallmark of multiple sclerosis (MS) disease, few studies focus on the mitochondria of immune cells. We aimed to compare the mitochondrial function of the peripheral blood mononuclear cells (PBMCs) from MS patients with (M+) and without (M−) lipid-specific oligoclonal immunoglobulin M bands (LS-OCMB), and healthydonors (HD). We conducted an exploratory cross-sectional study with 19 untreated MS patients (M+ = 9 and M− = 10) and 17 HDs. Mitochondrial superoxide anion production and mitochondrial mass in PBMCs were assessed without and with phytohemagglutinin by flow cytometry. The PBMCs’ mitochondrial function was analyzed using Seahorse technology. Superoxide anion production corrected by the mitochondrial mass was higher in MS patients compared with HDs (<i>p</i> = 0.011). Mitochondrial function from M+ patients showed some impairments compared with M− patients. Without stimulus, we observed higher proton leak (<i>p</i> = 0.041) but lower coupling efficiency (<i>p</i> = 0.041) in M+ patients; and under stimulation, lower metabolic potential ECAR (<i>p</i> = 0.011), and lower stressed OCR/ECAR in the same patients. Exclusively among M+ patients, we described a higher mitochondrial dysfunction in the oldest ones. The mitochondrial impairments found in the PBMCs from MS patients, specifically in M+ patients, could help to better understand the disease’s physiopathology.
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spelling doaj.art-f2e9aa44cc2d4b8e909fd0f8a2459c142023-11-24T03:48:36ZengMDPI AGBiology2079-77372022-11-011111163310.3390/biology11111633Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis PatientsMaría Inmaculada Domínguez-Mozo0María Celeste García-Frontini Nieto1María Isabel Gómez-Calcerrada2Silvia Pérez-Pérez3María Ángel García-Martínez4Luisa María Villar5Noelia Villarrubia6Lucienne Costa-Frossard7Rafael Arroyo8Roberto Alvarez-Lafuente9Environmental Factors in Degenerative Diseases Research Group, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainEnvironmental Factors in Degenerative Diseases Research Group, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainEnvironmental Factors in Degenerative Diseases Research Group, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainEnvironmental Factors in Degenerative Diseases Research Group, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainEnvironmental Factors in Degenerative Diseases Research Group, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainDepartment of Immunology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28040 Madrid, SpainDepartment of Immunology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28040 Madrid, SpainDepartment of Neurology, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, SpainDepartment of Neurology, Hospital Universitario Quironsalud Madrid, 28223 Madrid, SpainEnvironmental Factors in Degenerative Diseases Research Group, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, SpainAlthough impaired mitochondrial function has been proposed as a hallmark of multiple sclerosis (MS) disease, few studies focus on the mitochondria of immune cells. We aimed to compare the mitochondrial function of the peripheral blood mononuclear cells (PBMCs) from MS patients with (M+) and without (M−) lipid-specific oligoclonal immunoglobulin M bands (LS-OCMB), and healthydonors (HD). We conducted an exploratory cross-sectional study with 19 untreated MS patients (M+ = 9 and M− = 10) and 17 HDs. Mitochondrial superoxide anion production and mitochondrial mass in PBMCs were assessed without and with phytohemagglutinin by flow cytometry. The PBMCs’ mitochondrial function was analyzed using Seahorse technology. Superoxide anion production corrected by the mitochondrial mass was higher in MS patients compared with HDs (<i>p</i> = 0.011). Mitochondrial function from M+ patients showed some impairments compared with M− patients. Without stimulus, we observed higher proton leak (<i>p</i> = 0.041) but lower coupling efficiency (<i>p</i> = 0.041) in M+ patients; and under stimulation, lower metabolic potential ECAR (<i>p</i> = 0.011), and lower stressed OCR/ECAR in the same patients. Exclusively among M+ patients, we described a higher mitochondrial dysfunction in the oldest ones. The mitochondrial impairments found in the PBMCs from MS patients, specifically in M+ patients, could help to better understand the disease’s physiopathology.https://www.mdpi.com/2079-7737/11/11/1633mitochondriamultiple sclerosislipid-specific oligoclonal immunoglobulin M bands (LS-OCMB)
spellingShingle María Inmaculada Domínguez-Mozo
María Celeste García-Frontini Nieto
María Isabel Gómez-Calcerrada
Silvia Pérez-Pérez
María Ángel García-Martínez
Luisa María Villar
Noelia Villarrubia
Lucienne Costa-Frossard
Rafael Arroyo
Roberto Alvarez-Lafuente
Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients
Biology
mitochondria
multiple sclerosis
lipid-specific oligoclonal immunoglobulin M bands (LS-OCMB)
title Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients
title_full Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients
title_fullStr Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients
title_full_unstemmed Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients
title_short Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients
title_sort mitochondrial impairments in peripheral blood mononuclear cells of multiple sclerosis patients
topic mitochondria
multiple sclerosis
lipid-specific oligoclonal immunoglobulin M bands (LS-OCMB)
url https://www.mdpi.com/2079-7737/11/11/1633
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