Synaptic and nonsynaptic mitochondria demonstrate a different degree of calcium-induced mitochondrial dysfunction

Yarana, Chontida; Sanit, Jantira; Chattipakorn, Nipon; Chattipakorn, Siriporn C.

doi:10.1016/j.lfs.2012.04.004

Cited by 30 publications

(14 citation statements)

References 59 publications

(64 reference statements)

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“…Other studies have suggested that mitochondria play an integral role in Aβ-induced Ca 2+ dyshomeostasis and toxicity via a mechanism involving Ca 2+ mito overload, dissipation of ΔΨm, mPTP opening, and impairment of store-operated Ca 2+ entry to replenish depleted internal Ca 2+ stores [18, 23, 32, 33, 38]. Since approximately half of all mitochondria in cells are localized to microdomains of high Ca 2+ cyt , they are highly susceptible to Ca 2+ -induced injury [22, 30, 38].…”

Section: Discussionmentioning

confidence: 99%

“…Since approximately half of all mitochondria in cells are localized to microdomains of high Ca 2+ cyt , they are highly susceptible to Ca 2+ -induced injury [22, 30, 38]. Because mitochondrial dysfunction and Ca 2+ dyshomeostasis are inextricably intertwined in AD, we investigated the contribution of tau and Aβ to these pathologic phenomena.…”

Section: Discussionmentioning

confidence: 99%

“…Elevated Ca 2+ cyt is known to induce rapid Ca 2+ uptake by mitochondria in microdomains of high Ca 2+ cyt that exist near Ca 2+ channels on the plasma membrane and ryanodine receptors on the endoplasmic reticulum (ER) [22, 30]. The resultant mitochondrial Ca 2+ (Ca 2+ mito ) overload can cause depolarization of ΔΨm, increased ROS production, opening of the mitochondrial permeability transition pore (mPTP), and mitochondrial swelling - especially in synaptic mitochondria, which are more likely to exist in high Ca 2+ cyt microdomains [13, 38]. Furthermore, a recent study found Aβ 42 oligomers cause Ca 2+ influx into primary rat neurons from cortex, hippocampus, and cerebellum, which leads to Ca 2+ mito overload, mPTP opening, and cell death [32].…”

Section: Introductionmentioning

confidence: 99%

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Tau facilitates Aβ-induced loss of mitochondrial membrane potential independent of cytosolic calcium fluxes in mouse cortical neurons

Pallo

Johnson

2015

Neuroscience Letters

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Alzheimer’s disease (AD) is defined by presence of two pathological hallmarks, the intraneuronal neurofibrillary tangle (NFT) formed by abnormally processed tau, and the extracellular amyloid plaques formed primarily by the amyloid beta peptide (Aβ). In AD it is likely that these two proteins act in concert to impair neuronal function, and there is evidence to suggest that one of the key targets on which they converge is the mitochondria. For example, overexpression of a pathologic form of tau in rat primary cortical neurons exacerbates Aβ-induced mitochondrial membrane potential (ΔΨm) loss due to impairment of the calcium (Ca2+) buffering capability of mitochondria. However the role of physiological levels of tau in mediating Aβ-induced mitochondrial dysfunction was not examined. Therefore in this present study we used primary neurons from wild type (WT) and tau knockout (tau−/−) mice to investigate whether endogenous tau facilitates Aβ–induced ΔΨm loss and alterations in cytosolic calcium (Ca2+cyt). Knocking out tau significantly protected mouse primary cortical neurons from loss of ΔΨm caused by low concentrations of Aβ42, which supports our previous findings. However, the absence of tau resulted in significantly greater increases in Ca2+cyt in response to Aβ treatment when compared to those observed in WT mouse primary cortical neurons. This unexpected outcome may be explained by findings that suggest tau−/− neurons display certain phenotypic abnormalities associated with alterations in Ca2+cyt. Overall, data indicate that tau facilitates Aβ-induced mitochondrial dysfunction and this effect is independent of Aβ-induced alterations in Ca2+cyt.1

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tau facilitates Aβ-induced loss of mitochondrial membrane potential independent of cytosolic calcium fluxes in mouse cortical neurons

Pallo

Johnson

2015

Neuroscience Letters

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“…Interestingly, synaptic mitochondria appear to have a lower threshold for calcium uptake before their membrane potential collapses, and mitochondrial function is impaired relative to their non-synaptic counterparts [ 36 ]. Overall, synaptic mitochondria appear to be more susceptible to calcium overload and respiratory chain complex dysfunction compared to mitochondria of non-synaptic origin.…”

Section: Calcium Bufferingmentioning

confidence: 96%

Mitochondria, the Synapse, and Neurodegeneration

Chrysostomou¹,

Turnbull

2016

Mitochondrial Dysfunction in Neurodegenerative Disorders

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Mitochondria have a remarkably sophisticated structure and essential function within neurons that ensure normal synaptic transmission and maintained synaptic plasticity and hence normal information processing that can occur within the brain. The importance of mitochondria for synaptic structural preservation and activity is exemplifi ed by a high mitochondrial density at synaptic sites, whereas synaptic mitochondrial dysfunction or loss of mitochondria from synapses leads to synaptic abnormalities. The increasing body of evidence for mitochondrial defects, early synaptic dysfunction, and/or decreased synaptic density in common neurodegenerative disorders places these organelles at centre stage and establishes synaptic mitochondria as good candidates for drug targeting. In this chapter, we describe synaptic mitochondrial functions and present the evidence for synaptic disturbances in common neurodegenerative and mitochondrial diseases. Finally, we discuss the proposed mechanisms of neuronal loss with a focus on early synaptic loss. Keywords Neurons and MitochondriaThe highly specialized neuronal morphology allows neurons to form networks that control and facilitate all the information processing that occurs within the brain. Information is conveyed from one neuron to another via synaptic transmission, a process that is highly dependent on mitochondrial function. Hence, mitochondrial

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“…These molecules contribute toward the adverse effects of CS, playing key roles in lung cancer (Houghton et al, 2008;Khan et al, 2008;Mouded et al, 2009). Previously, it was suggested that the 18 kDa translocator protein (TSPO) may protect cells from damage induced by free radicals (Gatliff and Campanella, 2012;Joo et al, 2012;Lehtonen et al, 2012;Maulik and Kumar, 2012;Veenman and Gavish, 2012;Yarana et al, 2012;Zeno et al, 2012;de Tassigny et al, 2013;Thompson et al, 2013;Mitra et al, 2014). TSPO and its closely associated protein voltagedependent anion channel (VDAC) are involved in essential functions related to tumorigenicity, such as apoptosis and regulation of the mitochondrial membrane potential.…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke effects on TSPO and VDAC expression in a cellular lung cancer model

Gavish¹,

Cohen²,

Nagler³

2016

European Journal of Cancer Prevention

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As redox iron and copper ions are found in lung pleural fluid and parenchyma, we aimed to examine the effect of cigarette smoke (CS) alone and the combined effects of CS and redox metals, iron and copper ions, containing medium (saliva), on epithelial H1299 lung cancer cells. We also examined the expression levels of the anticarcinogenic and proapoptotic 18 kDa translocator protein (TSPO) and its closely associated protein voltage-dependent anion channel (VDAC). H1299 cells were subjected to western blot analysis using anti-TSPO and anti-VDAC antibodies. With the former, the 18 kDa band appeared as expected and a 72 kDa band also appeared. It may be assumed that in H1299 lung cancer cells, an additional form of TSPO protein appears as a four-unit tetrameric complex, which is affected by CS exposure. A significant decrease in the expression level of the 72 kDa protein occurred following only 60 min of CS exposure, whereas VDAC protein levels were increased following only 30 min of CS exposure. These results, together with our previous related studies, suggest a comprehensive two-arm novel paradigm for lung cancer induced by CS, and mediated by an altered TSPO protein, possibly resulting from both the 72 kDa TSPO degradation and redox metal ion-induced enhancement of free radical attack. We suggest that both of the most important proapoptotic and anticancer proteins, p53 and TSPO, are damaged by CS, paving the way for lung cancer initiation and progression.

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Synaptic and nonsynaptic mitochondria demonstrate a different degree of calcium-induced mitochondrial dysfunction

Cited by 30 publications

References 59 publications

Tau facilitates Aβ-induced loss of mitochondrial membrane potential independent of cytosolic calcium fluxes in mouse cortical neurons

Tau facilitates Aβ-induced loss of mitochondrial membrane potential independent of cytosolic calcium fluxes in mouse cortical neurons

Mitochondria, the Synapse, and Neurodegeneration

Cigarette smoke effects on TSPO and VDAC expression in a cellular lung cancer model

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