Affiliation:
1. Center for Aging and Associated Diseases, Helmy Institute of Medical Sciences, Zewail City of Science and Technology, Giza, Egypt
Abstract
Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX) enzymatic activity. Here we determined mitochondrial as well as NOX-dependent rates of oxygen consumption in parallel with H2O2generation in freshly isolated synaptosomes using high resolution respirometry combined with fluorescence or electrochemical sensory. Our results indicate that although synaptic mitochondria exhibit substantially higher respiratory activities (8–82-fold greater than NOX oxygen consumption depending on mitochondrial respiratory state), NADPH-dependent oxygen consumption is associated with greater H2O2production (6-7-fold higher NOX-H2O2). We also show that, in terms of the consumed oxygen, while synaptic mitochondria “leaked”0.71%±0.12H2O2during NAD+-linked resting,0.21%±0.04during NAD+-linked active respiration, and0.07%±0.02during FAD+-linked active respiration, NOX converted38%±13of O2into H2O2. Our results indicate that NOX rather than mitochondria is the major source of synaptic H2O2. The present approach may assist in the identification of redox-modulating synaptic factors that underlie a variety of physiological and pathological processes in neurons.
Funder
Science and Technology Development Fund, Egypt
Subject
Cell Biology,Aging,General Medicine,Biochemistry
Cited by
16 articles.
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