Oxidative Metabolism, Mitochondrial Damage and Neurodegenerative Disease: A Complex Triumvirat

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 8852

Special Issue Editors

Research Center on Animal Cognition, CNRS UMR 5169 (bat 4R4) cours Rosalind Franklin, Center of Integrative Biology, Université Toulouse 3, Paul Sabatier118 route de Narbonne, 31062 Toulouse, CEDEX 09, France
Interests: mathematical modeling; mitochondria; reactive oxygen species; aging; neurodegenerative processes; oxidative metabolism
Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS UMR5169, UPS, 31062 Toulouse, France
Interests: depression; metabolism; aging; antidepressant; monoamines; astrocytes

Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS) are derived forms of atmospheric oxygen with additional electron(s). ROS most likely appeared on Earth together with the first atmospheric oxygen molecules about 2.4–3.8 billion years ago. As signaling molecules, ROS are versatile owing to their diverse properties, and can push the cells or organisms to enter oxidative stress if they are not balanced by antioxidant machinery. Thus, there is a balance between ROS production and antioxidant defenses which is highly regulated. Mitochondria are a key player of this equilibrium, and the major provider of ROS in the cell. In the last decade, evidence has emerged of a direct link between mitochondrial status and the neurodegenerative processes detected in pathologies such as, but not limited to, Parkinson syndrome, Alzheimer’s disease, and optic atrophies.

In this issue, we will explore the different sides of this triumvirate linking oxidative stress, mitochondria, and neurodegenerative diseases. We will collect articles from mathematical to integrative in vitro/in vivo models ranging from molecular to behavioral levels toward analyzing the latest research in the field. 

Prof. Noelie Davezac
Prof. Bruno Pierre Guiard
Guest Editors

Manuscript Submission Information

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Keywords

  • reactive oxygen species
  • mitochondria
  • neurodegenerative processes
  • mathematical modelling
  • oxidative stress
  • systems biology
  • brain
  • plasticity

Published Papers (3 papers)

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Research

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18 pages, 9473 KiB  
Article
Mitochondrial Calcium-Triggered Oxidative Stress and Developmental Defects in Dopaminergic Neurons Differentiated from Deciduous Teeth-Derived Dental Pulp Stem Cells with MFF Insufficiency
by Xiao Sun, Shuangshan Dong, Hiroki Kato, Jun Kong, Yosuke Ito, Yuta Hirofuji, Hiroshi Sato, Takahiro A. Kato, Yasunari Sakai, Shouichi Ohga, Satoshi Fukumoto and Keiji Masuda
Antioxidants 2022, 11(7), 1361; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11071361 - 13 Jul 2022
Cited by 6 | Viewed by 3108
Abstract
Mitochondrial fission factor (MFF) is an adapter that targets dynamin-related protein 1 from the cytosol to the mitochondria for fission. Loss-of-function MFF mutations cause encephalopathy due to defective mitochondrial and peroxisomal fission 2 (EMPF2). To elucidate the molecular mechanisms that were involved, we [...] Read more.
Mitochondrial fission factor (MFF) is an adapter that targets dynamin-related protein 1 from the cytosol to the mitochondria for fission. Loss-of-function MFF mutations cause encephalopathy due to defective mitochondrial and peroxisomal fission 2 (EMPF2). To elucidate the molecular mechanisms that were involved, we analyzed the functional effects of MFF depletion in deciduous teeth-derived dental pulp stem cells differentiating into dopaminergic neurons (DNs). When treated with MFF-targeting small interfering RNA, DNs showed impaired neurite outgrowth and reduced mitochondrial signals in neurites harboring elongated mitochondria. MFF silencing also caused mitochondrial Ca2+ accumulation through accelerated Ca2+ influx from the endoplasmic reticulum (ER) via the inositol 1,4,5-trisphosphate receptor. Mitochondrial Ca2+ overload led DNs to produce excessive reactive oxygen species (ROS), and downregulated peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1α). MFF was co-immunoprecipitated with voltage-dependent anion channel 1, an essential component of the ER-mitochondrial Ca2+ transport system. Folic acid supplementation normalized ROS levels, PGC-1α mediated mitochondrial biogenesis, and neurite outgrowth in MFF depleted DNs, without affecting their mitochondrial morphology or Ca2+ levels. We propose that MFF negatively regulates the mitochondrial Ca2+ influx from the ER. MFF-insufficiency recapitulated the EMPF2 neuropathology with increased oxidative stress and suppressed mitochondrial biogenesis. ROS and mitochondrial biogenesis might be potential therapeutic targets for EMPF2. Full article
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17 pages, 4855 KiB  
Article
CDDO-Me Attenuates CA1 Neuronal Death by Facilitating RalBP1-Mediated Mitochondrial Fission and 4-HNE Efflux in the Rat Hippocampus Following Status Epilepticus
by Ji-Eun Kim, Duk-Shin Lee, Tae-Hyun Kim and Tae-Cheon Kang
Antioxidants 2022, 11(5), 985; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11050985 - 18 May 2022
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Abstract
Ras-related protein Ral-A (RalA)-binding protein 1 (RalBP1, also known as Ral-interacting protein of 76 kDa (RLIP76) or Ral-interacting protein 1 (RLIP1 or RIP1)) is involved in the efflux of 4-hydroxynonenal (4-HNE, an end product of lipid peroxidation), as well as mitochondrial fission. In [...] Read more.
Ras-related protein Ral-A (RalA)-binding protein 1 (RalBP1, also known as Ral-interacting protein of 76 kDa (RLIP76) or Ral-interacting protein 1 (RLIP1 or RIP1)) is involved in the efflux of 4-hydroxynonenal (4-HNE, an end product of lipid peroxidation), as well as mitochondrial fission. In the present study, we found that 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) attenuated CA1 neuronal death and aberrant mitochondrial elongations in these neurons coupled with enhanced RalBP1 expression and reduced 4-HNE levels following status epilepticus (SE). RalBP1 knockdown did not affect mitochondrial dynamics and CA1 neuronal death under physiological and post-SE conditions. Following SE, however, cotreatment of RalBP1 siRNA diminished the effect of CDDO-Me on 4-HNE levels, mitochondrial hyperfusion in CA1 neurons, and CA1 neuronal death. These findings indicate that CDDO-Me may ameliorate CA1 neuronal death by facilitating RalBP1-mediated 4-HNE efflux and mitochondrial fission following SE. Therefore, our findings suggest that increased RalBP1 expression/activity may be one of the considerable targets to protect neurons from SE. Full article
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Review

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19 pages, 1458 KiB  
Review
The Alterations in Mitochondrial Dynamics Following Cerebral Ischemia/Reperfusion Injury
by Jirapong Vongsfak, Wasana Pratchayasakul, Nattayaporn Apaijai, Tanat Vaniyapong, Nipon Chattipakorn and Siriporn C. Chattipakorn
Antioxidants 2021, 10(9), 1384; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10091384 - 30 Aug 2021
Cited by 34 | Viewed by 3767
Abstract
Cerebral ischemia results in a poor oxygen supply and cerebral infarction. Reperfusion to the ischemic area is the best therapeutic approach. Although reperfusion after ischemia has beneficial effects, it also causes ischemia/reperfusion (I/R) injury. Increases in oxidative stress, mitochondrial dysfunction, and cell death [...] Read more.
Cerebral ischemia results in a poor oxygen supply and cerebral infarction. Reperfusion to the ischemic area is the best therapeutic approach. Although reperfusion after ischemia has beneficial effects, it also causes ischemia/reperfusion (I/R) injury. Increases in oxidative stress, mitochondrial dysfunction, and cell death in the brain, resulting in brain infarction, have also been observed following cerebral I/R injury. Mitochondria are dynamic organelles, including mitochondrial fusion and fission. Both processes are essential for mitochondrial homeostasis and cell survival. Several studies demonstrated that an imbalance in mitochondrial dynamics after cerebral ischemia, with or without reperfusion injury, plays an important role in the regulation of cell survival and infarct area size. Mitochondrial dysmorphology/dysfunction and inflammatory processes also occur after cerebral ischemia. Knowledge surrounding the mechanisms involved in the imbalance in mitochondrial dynamics following cerebral ischemia with or without reperfusion injury would help in the prevention or treatment of the adverse effects of cerebral injury. Therefore, this review aims to summarize and discuss the roles of mitochondrial dynamics, mitochondrial function, and inflammatory processes in cerebral ischemia with or without reperfusion injury from in vitro and in vivo studies. Any contradictory findings are incorporated and discussed. Full article
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