scholarly journals Established Principles and Emerging Concepts on the Interplay between Mitochondrial Physiology andS-(De)nitrosylation: Implications in Cancer and Neurodegeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Giuseppina Di Giacomo ◽  
Salvatore Rizza ◽  
Costanza Montagna ◽  
Giuseppe Filomeni
Keyword(s):  
Nitric Oxide ◽  
Posttranslational Modification ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cellular Processes ◽  
Mitochondrial Homeostasis ◽  
Mitochondrial Functions ◽  
Related Proteins

S-nitrosylation is a posttranslational modification of cysteine residues that has been frequently indicated as potential molecular mechanism governing cell response upon redox unbalance downstream of nitric oxide (over)production. In the last years, increased levels ofS-nitrosothiols (SNOs) have been tightly associated with the onset of nitroxidative stress-based pathologies (e.g., cancer and neurodegeneration), conditions in which alterations of mitochondrial homeostasis and activation of cellular processes dependent on it have been reported as well. In this paper we aim at summarizing the current knowledge of mitochondria-related proteins undergoingS-nitrosylation and how this redox modification might impact on mitochondrial functions, whose impairment has been correlated to tumorigenesis and neuronal cell death. In particular, emphasis will be given to the possible, but still neglected implication of denitrosylation reactions in the modulation of mitochondrial SNOs and how they can affect mitochondrion-related cellular process, such as oxidative phosphorylation, mitochondrial dynamics, and mitophagy.

scholarly journals Nitric Oxide-induced Activation of the Type 1 Ryanodine Receptor Is Critical for Epileptic Seizure-induced Neuronal Cell Death

EBioMedicine ◽  
2016 ◽  
Vol 11 ◽  
pp. 253-261 ◽  
Author(s):  
Yoshinori Mikami ◽  
Kazunori Kanemaru ◽  
Yohei Okubo ◽  
Takuya Nakaune ◽  
Junji Suzuki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Ryanodine Receptor ◽  
Epileptic Seizure ◽  
Neuronal Cell Death ◽  
Neuronal Cell

The role of nitric oxide and PARP in neuronal cell death

2005 ◽  
pp. 146-156
Author(s):  
Mika Shimoji ◽  
Valina L. Dawson ◽  
Ted M. Dawson
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Mitochondrial Quality Control Mechanisms and the PHB (Prohibitin) Complex

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 238 ◽  
Author(s):  
Blanca Hernando-Rodríguez ◽  
Marta Artal-Sanz
Keyword(s):  
Quality Control ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Stress Responses ◽  
Membrane Lipids ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Gene ◽  
Control Mechanisms ◽  
Mitochondrial Homeostasis ◽  
Mitochondrial Functions

Mitochondrial functions are essential for life, critical for development, maintenance of stem cells, adaptation to physiological changes, responses to stress, and aging. The complexity of mitochondrial biogenesis requires coordinated nuclear and mitochondrial gene expression, owing to the need of stoichiometrically assemble the oxidative phosphorylation (OXPHOS) system for ATP production. It requires, in addition, the import of a large number of proteins from the cytosol to keep optimal mitochondrial function and metabolism. Moreover, mitochondria require lipid supply for membrane biogenesis, while it is itself essential for the synthesis of membrane lipids. To achieve mitochondrial homeostasis, multiple mechanisms of quality control have evolved to ensure that mitochondrial function meets cell, tissue, and organismal demands. Herein, we give an overview of mitochondrial mechanisms that are activated in response to stress, including mitochondrial dynamics, mitophagy and the mitochondrial unfolded protein response (UPRmt). We then discuss the role of these stress responses in aging, with particular focus on Caenorhabditis elegans. Finally, we review observations that point to the mitochondrial prohibitin (PHB) complex as a key player in mitochondrial homeostasis, being essential for mitochondrial biogenesis and degradation, and responding to mitochondrial stress. Understanding how mitochondria responds to stress and how such responses are regulated is pivotal to combat aging and disease.

scholarly journals Peroxiredoxin 5 Inhibits Glutamate-Induced Neuronal Cell Death through the Regulation of Calcineurin-Dependent Mitochondrial Dynamics in HT22 Cells

2019 ◽  
Vol 39 (20) ◽  
Author(s):  
Mi Hye Kim ◽  
Hong Jun Lee ◽  
Sang-Rae Lee ◽  
Hyun-Shik Lee ◽  
Jae-Won Huh ◽  
...  
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glutamate Toxicity ◽  
Ht22 Cells ◽  
Peroxidase Enzyme ◽  
The Central Nervous System

ABSTRACT Glutamate is an essential neurotransmitter in the central nervous system (CNS). However, high glutamate concentrations can lead to neurodegenerative diseases. A hallmark of glutamate toxicity is high levels of reactive oxygen species (ROS), which can trigger Ca2+ influx and dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Peroxiredoxin 5 (Prx5) is a well-known cysteine-dependent peroxidase enzyme. However, the precise effects of Prx5 on glutamate toxicity are still unclear. In this study, we investigated the role of Prx5 in glutamate-induced neuronal cell death. We found that glutamate treatment induces endogenous Prx5 expression and Ca2+/calcineurin-dependent dephosphorylation of Drp1, resulting in mitochondrial fission and neuronal cell death. Our results indicate that Prx5 inhibits glutamate-induced mitochondrial fission through the regulation of Ca2+/calcineurin-dependent dephosphorylation of Drp1, and it does so by scavenging cytosolic and mitochondrial ROS. Therefore, we suggest that Ca2+/calcineurin-dependent mitochondrial dynamics are deeply associated with glutamate-induced neurotoxicity. Consequently, Prx5 may be used as a potential agent for developing therapies against glutamate-induced neurotoxicity and neurodegenerative diseases where it plays a key role.

719 Protection by tetrahydrobiopterin from nitric oxide-induced neuronal cell death

1996 ◽  
Vol 25 ◽  
pp. S85
Author(s):  
Kunio Koshimura ◽  
Junko Tanaka ◽  
Yoshio Murakami ◽  
Yuzuru Kato
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Functional Interplay between Cristae Biogenesis, Mitochondrial Dynamics and Mitochondrial DNA Integrity

2019 ◽  
Vol 20 (17) ◽  
pp. 4311 ◽  
Author(s):  
Arun Kumar Kondadi ◽  
Ruchika Anand ◽  
Andreas S. Reichert
Keyword(s):  
Mitochondrial Dna ◽  
Unique Feature ◽  
Mitochondrial Dynamics ◽  
Human Diseases ◽  
Dna Integrity ◽  
Cellular Processes ◽  
The Past ◽  
Mitochondrial Structure ◽  
Mitochondrial Functions ◽  
Cellular Organelles

Mitochondria are vital cellular organelles involved in a plethora of cellular processes such as energy conversion, calcium homeostasis, heme biogenesis, regulation of apoptosis and ROS reactive oxygen species (ROS) production. Although they are frequently depicted as static bean-shaped structures, our view has markedly changed over the past few decades as many studies have revealed a remarkable dynamicity of mitochondrial shapes and sizes both at the cellular and intra-mitochondrial levels. Aberrant changes in mitochondrial dynamics and cristae structure are associated with ageing and numerous human diseases (e.g., cancer, diabetes, various neurodegenerative diseases, types of neuro- and myopathies). Another unique feature of mitochondria is that they harbor their own genome, the mitochondrial DNA (mtDNA). MtDNA exists in several hundreds to thousands of copies per cell and is arranged and packaged in the mitochondrial matrix in structures termed mt-nucleoids. Many human diseases are mechanistically linked to mitochondrial dysfunction and alteration of the number and/or the integrity of mtDNA. In particular, several recent studies identified remarkable and partly unexpected links between mitochondrial structure, fusion and fission dynamics, and mtDNA. In this review, we will provide an overview about these recent insights and aim to clarify how mitochondrial dynamics, cristae ultrastructure and mtDNA structure influence each other and determine mitochondrial functions.

scholarly journals Isoflavones Induce BEX2-Dependent Autophagy to Prevent ATR-Induced Neurotoxicity in SH-SY5Y Cells

2017 ◽  
Vol 43 (5) ◽  
pp. 1866-1879 ◽  
Author(s):  
Peng Li ◽  
Kun Ma ◽  
Hao-Yu Wu ◽  
Yan-Ping Wu ◽  
Bai-Xiang Li
Keyword(s):  
Cell Death ◽  
Neuronal Apoptosis ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Green Tea Polyphenols ◽  
Key Factors ◽  
Related Proteins ◽  
Catabolic Process ◽  
Plant Compounds

Background/Aims: Atrazine (ATR) is a broad-spectrum herbicide in wide use around the world. However, ATR is neurotoxic and can cause cell death in dopaminergic neurons, leading to neurodegenerative disorders. Autophagy is the basic cellular catabolic process involving the degradation of proteins and damaged organelles. Studies have shown that certain plant compounds can induce autophagy and prevent neuronal cell death. This prompted us to investigate plant compounds that might reduce the neurotoxic effects of ATR. Methods: By CCK-8 and flow cytometry, we tested the ability of five candidate compounds—isoflavones, resveratrol, quercetin, curcumin, and green tea polyphenols—to protect cells from ATR. Changes in the expression of tyrosine hydroxylase (TH) and brain-expressed X-linked 2 (BEX2), autophagy-related proteins and key factors in mTOR signaling, were detected by Western blotting. Results: Isoflavones had the strongest activity against ATR-induced neuronal apoptosis. ATR reduced the expression of TH and BEX2, whereas isoflavones increased TH and BEX2 expression. In addition, ATR inhibited autophagy, whereas isoflavones induced autophagy through the accumulation of LC3-II and decreased expression of p62; this effect was abolished by 3-methyladenine (3-MA). Furthermore, BEX2 siRNA abolished isoflavone-mediated autophagy and neuroprotection in vitro. Conclusion: Isoflavones activate BEX2-dependent autophagy, protecting against ATR-induced neuronal apoptosis.

scholarly journals Mechanisms of Neuronal Protection against Excitotoxicity, Endoplasmic Reticulum Stress, and Mitochondrial Dysfunction in Stroke and Neurodegenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Howard Prentice ◽  
Jigar Pravinchandra Modi ◽  
Jang-Yen Wu
Keyword(s):  
Nitric Oxide ◽  
Endoplasmic Reticulum ◽  
Nmda Receptor ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Permeability Transition ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Calcium Overload

In stroke and neurodegenerative disease, neuronal excitotoxicity, caused by increased extracellular glutamate levels, is known to result in calcium overload and mitochondrial dysfunction. Mitochondrial deficits may involve a deficiency in energy supply as well as generation of high levels of oxidants which are key contributors to neuronal cell death through necrotic and apoptotic mechanisms. Excessive glutamate receptor stimulation also results in increased nitric oxide generation which can be detrimental to cells as nitric oxide interacts with superoxide to form the toxic molecule peroxynitrite. High level oxidant production elicits neuronal apoptosis through the actions of proapoptotic Bcl-2 family members resulting in mitochondrial permeability transition pore opening. In addition to apoptotic responses to severe stress, accumulation of misfolded proteins and high levels of oxidants can elicit endoplasmic reticulum (ER) stress pathways which may also contribute to induction of apoptosis. Two categories of therapeutics are discussed that impact major pro-death events that include induction of oxidants, calcium overload, and ER stress. The first category of therapeutic agent includes the amino acid taurine which prevents calcium overload and is also capable of preventing ER stress by inhibiting specific ER stress pathways. The second category involves N-methyl-D-aspartate receptor (NMDA receptor) partial antagonists illustrated by S-Methyl-N, N-diethyldithiocarbamate sulfoxide (DETC-MeSO), and memantine. DETC-MeSO is protective through preventing excitotoxicity and calcium overload and by blocking specific ER stress pathways. Another NMDA receptor partial antagonist is memantine which prevents excessive glutamate excitation but also remarkably allows maintenance of physiological neurotransmission. Targeting of these major sites of neuronal damage using pharmacological agents is discussed in terms of potential therapeutic approaches for neurological disorders.

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