Regulation of brain mitochondrial H2O2 production by membrane potential and NAD(P)H redox state
Anatoly A. Starkov,Gary Fiskum +1 more
TLDR
Findings indicate that ROS production by mitochondria oxidizing physiological NADH‐dependent substrates is regulated by ΔΨ and by the NAD(P)H redox state over ranges consistent with those that exist at different levels of cellular energy demand.Abstract:
Mitochondrial production of reactive oxygen species (ROS) at Complex I of the electron transport chain is implicated in the etiology of neural cell death in acute and chronic neurodegenerative disorders. However, little is known regarding the regulation of mitochondrial ROS production by NADH-linked respiratory substrates under physiologically realistic conditions in the absence of respiratory chain inhibitors. This study used Amplex Red fluorescence measurements of H2O2 to test the hypothesis that ROS production by isolated brain mitochondria is regulated by membrane potential (DeltaPsi) and NAD(P)H redox state. DeltaPsi was monitored by following the medium concentration of the lipophilic cation tetraphenylphosphonium with a selective electrode. NAD(P)H autofluorescence was used to monitor NAD(P)H redox state. While the rate of H2O2 production was closely related to DeltaPsi and the level of NAD(P)H reduction at high values of DeltaPsi, 30% of the maximal rate of H2O2 formation was still observed in the presence of uncoupler (p-trifluoromethoxycarbonylcyanide phenylhydrazone) concentrations that provided for maximum depolarization of DeltaPsi and oxidation of NAD(P)H. Our findings indicate that ROS production by mitochondria oxidizing physiological NADH-dependent substrates is regulated by DeltaPsi and by the NAD(P)H redox state over ranges consistent with those that exist at different levels of cellular energy demand.read more
Citations
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Journal ArticleDOI
How mitochondria produce reactive oxygen species.
TL;DR: The description outlined here facilitates the understanding of factors that favour mitochondrial ROS production and develops better methods to measure mitochondrial O2•− and H2O2 formation in vivo, as uncertainty about these values hampers studies on the role of mitochondrial ROS in pathological oxidative damage and redox signalling.
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Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release
TL;DR: The mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, and all of the known ROS-producing sites and their relevance to the mitochondrial ROS production in vivo are discussed.
Journal ArticleDOI
Calcium, ATP, and ROS: a mitochondrial love-hate triangle
TL;DR: A "two-hit" hypothesis is developed, in which Ca(2+) plus another pathological stimulus can bring about mitochondrial dysfunction, and the delicate balance between the positive and negative effects of Ca( 2+) and the signaling events that perturb this balance is highlighted.
Journal ArticleDOI
Mitochondrial metabolism of reactive oxygen species.
A. Yu. Andreyev,A. Yu. Andreyev,Yu. E. Kushnareva,Yu. E. Kushnareva,Anatoly A. Starkov,Anatoly A. Starkov +5 more
TL;DR: It is suggested that mitochondria augment intracellular oxidative stress due primarily to failure of their ROS removal systems, whereas the role of mitochondrial ROS emission is yet to be determined and a net increase in mitochondrial ROS production in situ remains to be demonstrated.
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Mechanisms of cell death in oxidative stress.
Stefan W. Ryter,Hong Pyo Kim,Alexander Hoetzel,Jeong W. Park,Kiichi Nakahira,Xue Wang,Augustine M.K. Choi +6 more
TL;DR: Cell death mechanisms have been studied across a broad spectrum of models of oxidative stress, including H2O2, nitric oxide and derivatives, endotoxin-induced inflammation, photodynamic therapy, ultraviolet-A and ionizing radiations, and cigarette smoke.
References
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TL;DR: The kinetics for uptake by mitochondria of TPP+ and DDA+ were analyzed, and it was found that TPP+ permeated the mitochondrial membrane about 15 times faster than DDA+.