Redox-dependent regulation of mitochondrial dynamics by DJ-1 paralogs in Saccharomyces cerevisiae

Bankapalli, Kondalarao; Vishwanathan, Vinaya; Susarla, Gautam; Ningaraju, S.; Saladi, SreeDivya; Peethambaram, Divya; D’Silva, Patrick

doi:10.1016/j.redox.2020.101451

Cited by 22 publications

(49 citation statements)

References 52 publications

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“…In consistent with our study, high respiration rates but decreased reserve capacity, as well as loss of mitochondrial membrane potential were induced by hydrogen peroxide and preceded mitochondrial fragmentation in mouse skeletal muscle myocytes [55]. Specifically, it has been found that prior to mitochondrial fragmentation, mitochondria elongate and fuse as an adaptive response to cellular insults, including ER stress and ROS generation [28,56]. Changes in mitochondrial structure have shown to determine cell fate when autophagy is stimulated, with elongated mitochondria being able to escape from degradation and maintain cell viability [57].…”

Section: Discussionsupporting

confidence: 90%

“…Previous studies have reported an increase in mitochondrial respiration and mass as an adaptive response to ER stress, which, when unresolved, leads to mitochondrial dysfunction and cell death [12,28,41]. A major finding of this study is that prolonged tunicamycin administration induced impaired mitochondrial function that was mediated by ROS generation.…”

Section: Discussionmentioning

confidence: 51%

“…Mitochondrial network structure was visualised using MitoTracker Red to explore mitochondrial dynamics, including fusion and fission processes, in response to ER stress and antioxidant intervention. Tunicamycin induced a significant increase in mitochondrial interconnectivity and elongation, indicative of mitochondrial fusion events, which can be associated with increased mitochondrial mass [27,28]. These results were accompanying with an increase in the percentage of cytosol occupied by mitochondria.…”

Section: Mitochondrial Morphology: Fusion and Fission Eventsmentioning

confidence: 95%

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Eukarion-134 Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction in Human Skeletal Muscle Cells

et al. 2020

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Maladaptive endoplasmic reticulum (ER) stress is associated with modified reactive oxygen species (ROS) generation and mitochondrial abnormalities; and is postulated as a potential mechanism involved in muscle weakness in myositis, an acquired autoimmune neuromuscular disease. This study investigates the impact of ROS generation in an in vitro model of ER stress in skeletal muscle, using the ER stress inducer tunicamycin (24 h) in the presence or absence of a superoxide dismutase/catalase mimetic Eukarion (EUK)-134. Tunicamycin induced maladaptive ER stress, which was mitigated by EUK-134 at the transcriptional level. ER stress promoted mitochondrial dysfunction, described by substantial loss of mitochondrial membrane potential, as well as a reduction in respiratory control ratio, reserve capacity, phosphorylating respiration, and coupling efficiency, which was ameliorated by EUK-134. Tunicamycin induced ROS-mediated biogenesis and fusion of mitochondria, which, however, had high propensity of fragmentation, accompanied by upregulated mRNA levels of fission-related markers. Increased cellular ROS generation was observed under ER stress that was prevented by EUK-134, even though no changes in mitochondrial superoxide were noticeable. These findings suggest that targeting ROS generation using EUK-134 can amend aspects of ER stress-induced changes in mitochondrial dynamics and function, and therefore, in instances of chronic ER stress, such as in myositis, quenching ROS generation may be a promising therapy for muscle weakness and dysfunction.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 51%

Section: Mitochondrial Morphology: Fusion and Fission Eventsmentioning

confidence: 95%

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Eukarion-134 Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction in Human Skeletal Muscle Cells

et al. 2020

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“…Previous studies have reported an increase in mitochondrial respiration and mass as an adaptive response to ER stress, which when unresolved, leads to mitochondrial dysfunction and cell death [13,26,39]. A major finding of this study is that prolonged tunicamycin administration induced impaired mitochondrial function that was mediated by ROS generation.…”

Section: Discussionmentioning

confidence: 51%

“…Mitochondrial network structure was visualised using MitoTracker Red to explore mitochondrial dynamics, including fusion and fission processes, in response to ER stress and antioxidant intervention. Tunicamycin induced a significant increase in mitochondrial interconnectivity and elongation, indicative of mitochondrial fusion events, which can be associated with increased mitochondrial mass [25,26]. These results were accompanying with an increase in the percentage of cytosol occupied by mitochondria.…”

Section: Mitochondrial Morphology: Fusion and Fission Eventsmentioning

confidence: 95%

Eukarion-134 attenuates endoplasmic reticulum stress-induced mitochondrial dysfunction in human skeletal muscle cells

Thoma

Lyon

Al-Shanti

et al. 2020

Preprint

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Maladaptive endoplasmic reticulum (ER) stress is associated with modified reactive oxygen species (ROS) generation, altered mitochondrial bioenergetics, and oxidative damage; and is postulated as a potential mechanism involved in the underlying muscle weakness experienced by patients with myositis, an acquired autoimmune neuromuscular disease. In this study, we investigate the impact of ROS generation in an in vitro model of ER stress in skeletal muscle, using the ER stress inducer tunicamycin (24 hours) in presence or absence of a superoxide dismutase/catalase mimetic Eukarion (EUK)-134. ER stress activation, ROS generation, mitochondrial function, biogenesis, morphology and dynamics (fusion/fission) were examined. Tunicamycin induced maladaptive ER stress, validated by stimulation of GRP94, GRP78, CHOP, XBP-1, ERDJ4, and GADD34, which were mostly mitigated by EUK-134 at transcriptional level. ER stress triggered mitochondrial unfolded protein response and promoted mitochondrial dysfunction, described by substantial loss of mitochondrial membrane potential, as well as reduction of respiratory control ratio, reserve capacity, phosphorylating respiration, and coupling efficiency, which was ameliorated by EUK-134. ROS-mediated biogenesis and fusion of mitochondria was evident in presence of tunicamycin, which however, had high propensity of fragmentation, accompanied by upregulated mRNA levels of fission-related markers. Increased cellular ROS generation oxidative stress was observed in response to ER stress that was ameliorated in the presence of EUK-134, even though no changes in mitochondrial superoxide were noticeable. These findings suggest that targeting ROS generation using the superoxide dismutase/catalase mimetic EUK-134 can amend aspects of ER stress-induced changes in mitochondrial dynamics and function. Overall, this study suggests that in instances of chronic ER stress, such as in myositis, quenching ROS generation may be a promising therapy for muscle weakness and dysfunction.

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Molecular Mechanisms of Degeneration in Parkinson’s Disease; Deep Brain Stimulation, Pluripotent Stem Cell Therapy, and Cutting Edge Technology in Treatment Of Parkinson’s Disease

Shah,

Tereda,

Mansour

2024

Curr Genet Med Rep

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Redox-dependent regulation of mitochondrial dynamics by DJ-1 paralogs in Saccharomyces cerevisiae

Cited by 22 publications

References 52 publications

Eukarion-134 Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction in Human Skeletal Muscle Cells

Eukarion-134 Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction in Human Skeletal Muscle Cells

Eukarion-134 attenuates endoplasmic reticulum stress-induced mitochondrial dysfunction in human skeletal muscle cells

Molecular Mechanisms of Degeneration in Parkinson’s Disease; Deep Brain Stimulation, Pluripotent Stem Cell Therapy, and Cutting Edge Technology in Treatment Of Parkinson’s Disease

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