Mitochondrial Electron Transport Chain Protein Abnormalities Detected in Plasma Extracellular Vesicles in Alzheimer’s Disease

Mitochondria provide energy to neurons through oxidative phosphorylation and eliminate Reactive Oxygen Species (ROS) through Superoxide Dismutase 1 (SOD1). Dysfunctional mitochondria, manifesting decreased activity of electron transport chain (ETC) complexes and high ROS levels, are involved in Alzh...

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Autores principales:	Pamela J. Yao, Erden Eren, Edward J. Goetzl, Dimitrios Kapogiannis
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	NADH oxidative phosphorylation Alzheimer’s disease mitochondria electron transport chain Superoxide Dismutase 1 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6e9b8bf684d8429490e04949e31be9b8
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spelling	oai:doaj.org-article:6e9b8bf684d8429490e04949e31be9b82021-11-25T16:49:21ZMitochondrial Electron Transport Chain Protein Abnormalities Detected in Plasma Extracellular Vesicles in Alzheimer’s Disease10.3390/biomedicines91115872227-9059https://doaj.org/article/6e9b8bf684d8429490e04949e31be9b82021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1587https://doaj.org/toc/2227-9059Mitochondria provide energy to neurons through oxidative phosphorylation and eliminate Reactive Oxygen Species (ROS) through Superoxide Dismutase 1 (SOD1). Dysfunctional mitochondria, manifesting decreased activity of electron transport chain (ETC) complexes and high ROS levels, are involved in Alzheimer’s disease (AD) pathogenesis. We hypothesized that neuronal mitochondrial dysfunction in AD is reflected in ETC and SOD1 levels and activity in plasma neuron-derived extracellular vesicles (NDEVs). We immunoprecipitated NDEVs targeting neuronal marker L1CAM from two cohorts: one including 22 individuals with early AD and 29 control subjects; and another including 14 individuals with early AD and 14 control subjects. In the first cohort, we measured levels of complexes I, III, IV, ATP synthase, and SOD1; in the second cohort, we measured levels and catalytic activity of complexes IV and ATP synthase. AD individuals had lower levels of complexes I (<i>p</i> < 0.0001), III (<i>p</i> < 0.0001), IV (<i>p</i> = 0.0061), and V (<i>p</i> < 0.0001), and SOD1 (<i>p</i> < 0.0001) compared to controls. AD individuals also had lower levels of catalytic activity of complex IV (<i>p</i> = 0.0214) and ATP synthase (<i>p</i> < 0.0001). NDEVs confirm quantitative and functional abnormalities in ECT complexes and SOD1 previously observed in AD models and during autopsy, opening the way for using them as biomarkers for mitochondrial dysfunction in AD.Pamela J. YaoErden ErenEdward J. GoetzlDimitrios KapogiannisMDPI AGarticleNADHoxidative phosphorylationAlzheimer’s diseasemitochondriaelectron transport chainSuperoxide Dismutase 1Biology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1587, p 1587 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NADH oxidative phosphorylation Alzheimer’s disease mitochondria electron transport chain Superoxide Dismutase 1 Biology (General) QH301-705.5
spellingShingle	NADH oxidative phosphorylation Alzheimer’s disease mitochondria electron transport chain Superoxide Dismutase 1 Biology (General) QH301-705.5 Pamela J. Yao Erden Eren Edward J. Goetzl Dimitrios Kapogiannis Mitochondrial Electron Transport Chain Protein Abnormalities Detected in Plasma Extracellular Vesicles in Alzheimer’s Disease
description	Mitochondria provide energy to neurons through oxidative phosphorylation and eliminate Reactive Oxygen Species (ROS) through Superoxide Dismutase 1 (SOD1). Dysfunctional mitochondria, manifesting decreased activity of electron transport chain (ETC) complexes and high ROS levels, are involved in Alzheimer’s disease (AD) pathogenesis. We hypothesized that neuronal mitochondrial dysfunction in AD is reflected in ETC and SOD1 levels and activity in plasma neuron-derived extracellular vesicles (NDEVs). We immunoprecipitated NDEVs targeting neuronal marker L1CAM from two cohorts: one including 22 individuals with early AD and 29 control subjects; and another including 14 individuals with early AD and 14 control subjects. In the first cohort, we measured levels of complexes I, III, IV, ATP synthase, and SOD1; in the second cohort, we measured levels and catalytic activity of complexes IV and ATP synthase. AD individuals had lower levels of complexes I (<i>p</i> < 0.0001), III (<i>p</i> < 0.0001), IV (<i>p</i> = 0.0061), and V (<i>p</i> < 0.0001), and SOD1 (<i>p</i> < 0.0001) compared to controls. AD individuals also had lower levels of catalytic activity of complex IV (<i>p</i> = 0.0214) and ATP synthase (<i>p</i> < 0.0001). NDEVs confirm quantitative and functional abnormalities in ECT complexes and SOD1 previously observed in AD models and during autopsy, opening the way for using them as biomarkers for mitochondrial dysfunction in AD.
format	article
author	Pamela J. Yao Erden Eren Edward J. Goetzl Dimitrios Kapogiannis
author_facet	Pamela J. Yao Erden Eren Edward J. Goetzl Dimitrios Kapogiannis
author_sort	Pamela J. Yao
title	Mitochondrial Electron Transport Chain Protein Abnormalities Detected in Plasma Extracellular Vesicles in Alzheimer’s Disease
title_short	Mitochondrial Electron Transport Chain Protein Abnormalities Detected in Plasma Extracellular Vesicles in Alzheimer’s Disease
title_full	Mitochondrial Electron Transport Chain Protein Abnormalities Detected in Plasma Extracellular Vesicles in Alzheimer’s Disease
title_fullStr	Mitochondrial Electron Transport Chain Protein Abnormalities Detected in Plasma Extracellular Vesicles in Alzheimer’s Disease
title_full_unstemmed	Mitochondrial Electron Transport Chain Protein Abnormalities Detected in Plasma Extracellular Vesicles in Alzheimer’s Disease
title_sort	mitochondrial electron transport chain protein abnormalities detected in plasma extracellular vesicles in alzheimer’s disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6e9b8bf684d8429490e04949e31be9b8
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_version_	1718412902692552704

Mitochondrial Electron Transport Chain Protein Abnormalities Detected in Plasma Extracellular Vesicles in Alzheimer’s Disease

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