Mitochondria and reactive oxygen species

Kowaltowski, Alicia J.; Souza-Pinto, Nadja C. de; Castilho, Roger F.; Vercesi, Anı́bal E.

doi:10.1016/j.freeradbiomed.2009.05.004

Cited by 962 publications

(649 citation statements)

References 231 publications

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“…8 At high tissue pO 2 (95%) respiration might become partially uncoupled making exact calculation of ATP production per mM oxygen extremely difficult. 21 Nevertheless, our data indicate a considerable contribution of presynaptic processes to energy demand of synaptic transmission. This might explain the critical dependence of fast spiking interneuron activity on oxidative metabolism, 9 despite the fact that energy demand of APs is close to the theoretical minimum.…”

Section: Discussionmentioning

confidence: 66%

Energy Demand of Synaptic Transmission at the Hippocampal Schaffer-Collateral Synapse

Liotta

Rösner

Huchzermeyer

et al. 2012

J Cereb Blood Flow Metab

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Neuroenergetic models of synaptic transmission predicted that energy demand is highest for action potentials (APs) and postsynaptic ion fluxes, whereas the presynaptic contribution is rather small. Here, we addressed the question of energy consumption at Schaffer-collateral synapses. We monitored stimulus-induced changes in extracellular potassium, sodium, and calcium concentration while recording partial oxygen pressure (pO 2 ) and NAD(P)H fluorescence. Blockade of postsynaptic receptors reduced ion fluxes as well as pO 2 and NAD(P)H transients by B50%. Additional blockade of transmitter release further reduced Na þ , K þ , and pO 2 transients by B30% without altering presynaptic APs, indicating considerable contribution of Ca 2 þ -removal, transmitter and vesicle turnover to energy consumption. Keywords: action potential; brain slice; electrophysiology; energy metabolism; evoked potentials; hippocampus INTRODUCTION Energy limitations determine the computational power and speed of neuronal systems. 1 Therefore, it is of critical importance to identify the energy demand associated with processes involved in neuronal computing such as synaptic transmission and action potential (AP) firing. Theoretical calculations on the basis of current kinetics in squid giant axons suggested that APs and postsynaptic ion fluxes rather than presynaptic processes determine energy consumption. 1,2 More recently, energy efficient AP generation and conduction was described in hippocampal mossy fibers. 3--5 Recalculating the energy need for APs suggests larger contribution of postsynaptic and presynaptic processes and transmitter uptake to the energy demand of synaptic transmission. 6,7 The authors predicted that in cerebral cortex, 50% of signaling associated energy is spent on restoration of ion fluxes at postsynaptic glutamate receptors, 21% is spent on APs, 20% on resting potentials, 5% and 4% on presynaptic transmitter release and transmitter recycling, respectively. However, such numbers have to be calculated or determined experimentally for each brain area in question as synaptic densities, receptor types, and ion channel expression differ for each particular signaling pathway. Journal of Cerebral BloodHere, we sought to determine the contribution of pre-and postsynaptic processes to changes in energy metabolism associated with glutamatergic and GABAergic transmission at the hippocampal Schaffer-collateral synapse that represents one of the best-studied connections in the archicortex. We monitored stimulus-induced changes in extracellular potassium, sodium, and calcium concentrations ([K þ ] o , [Na þ ] o , [Ca 2 þ ] o ) while recording tissue partial oxygen pressure (pO 2 ) and metabolism-related NAD(P)H transients. The energy demand of each single component of synaptic transmission

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Section: Discussionmentioning

confidence: 66%

Energy Demand of Synaptic Transmission at the Hippocampal Schaffer-Collateral Synapse

Liotta

Rösner

Huchzermeyer

et al. 2012

J Cereb Blood Flow Metab

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“…In addition, the electron transport chain via NADH produces NAD + and the decrease in mitochondrial NADH will contribute to the decline in mitochondrial NAD + . This decrease in NADH can also participate to mPTP opening as evidence shows that mitochondria are more susceptible to mPTP when the antioxidant power is exhausted (Kowaltowski, de Souza‐Pinto, Castilho, & Vercesi, 2009). …”

Section: Regulating Factors Of Mptp and Agingmentioning

confidence: 99%

Mitochondria and aging: A role for the mitochondrial transition pore?

2018

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SummaryThe cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging. Thus, mitochondrial ROS, oxidative damage, aging, and aging‐dependent diseases are strongly connected. However, other features of mitochondrial physiology and dysfunction have been recently implicated in the development of the aging process. Here, we examine the potential role of the mitochondrial permeability transition pore (mPTP) in normal aging and in aging‐associated diseases.

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“…Under normal conditions, calcium taken up by mitochondria can physiologically increase ATP generation by activating matrix dehydrogenases [141]. However, an increase in mitochondrial calcium can promote ROS and d NO generation and promote the loss of cytochrome c due to the mitochondrial permeability transition, which can result in increased mitochondrial ROS release [142]. Mitochondrial buffering of calcium may be impaired in PD, as suggested by reduced carbonyl cyanide m-chlorophenylhydrazone-releasable calcium in PD cybrids [143].…”

Section: Excitotoxicity Leading To Mitochondrial Dysfunction and Oxidmentioning

confidence: 99%

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Perfeito

Cunha‐Oliveira

Rego

2013

Free Radical Biology and Medicine

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a b s t r a c tParkinson disease (PD) is a chronic and progressive neurological disease associated with a loss of dopaminergic neurons. In most cases the disease is sporadic but genetically inherited cases also exist. One of the major pathological features of PD is the presence of aggregates that localize in neuronal cytoplasm as Lewy bodies, mainly composed of a-synuclein (a-syn) and ubiquitin. The selective degeneration of dopaminergic neurons suggests that dopamine itself may contribute to the neurodegenerative process in PD. Furthermore, mitochondrial dysfunction and oxidative stress constitute key pathogenic events of this disorder. Thus, in this review we give an actual perspective to classical pathways involving these two mechanisms of neurodegeneration, including the role of dopamine in sporadic and familial PD, as well as in the case of abuse of amphetamine-type drugs. Mutations in genes related to familial PD causing autosomal dominant or recessive forms may also have crucial effects on mitochondrial morphology, function, and oxidative stress. Environmental factors, such as MPTP and rotenone, have been reported to induce selective degeneration of the nigrostriatal pathways leading to a-syn-positive inclusions, possibly by inhibiting mitochondrial complex I of the respiratory chain and subsequently increasing oxidative stress. Recently, increased risk for PD was found in amphetamine users. Amphetamine drugs have effects similar to those of other environmental factors for PD, because long-term exposure to these drugs leads to dopamine depletion. Moreover, amphetamine neurotoxicity involves a-syn aggregation, mitochondrial dysfunction, and oxidative stress. Therefore, dopamine and related oxidative stress, as well as mitochondrial dysfunction, seem to be common links between PD and amphetamine neurotoxicity.

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Mitochondria and reactive oxygen species

Cited by 962 publications

References 231 publications

Energy Demand of Synaptic Transmission at the Hippocampal Schaffer-Collateral Synapse

Energy Demand of Synaptic Transmission at the Hippocampal Schaffer-Collateral Synapse

Mitochondria and aging: A role for the mitochondrial transition pore?

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

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