PA2G4/EBP1 ubiquitination by PRKN/PARKIN promotes mitophagy protecting neuron death in cerebral ischemia

Hwang, Inwoo; Kim, Byeong-Seong; Lee, Ho Yun; Cho, Sung-Woo; Lee, Seung Eun; Ahn, Jee-Yin

doi:10.1080/15548627.2023.2259215

Cited by 10 publications

(3 citation statements)

References 63 publications

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“…In one of them, memantine, a NMDA antagonist, was found to overcome the effect of CCCP on MTs [ 20 ], while in another study, CCCP affected mitophagy, a critical mechanism for restoring MT functions [ 21 ]. Interestingly, another recent study suggested [ 26 ] that CCCP can be used as a mitophagy promoter, which enhances cell survival. This could contradict our previous [ 19 ], current, and others’ [ 27 , 28 , 29 ] results.…”

Section: Discussionmentioning

confidence: 99%

Cultured Rat Hippocampal Neurons Exposed to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Undergo a Rapid, Presenilin-Dependent Change in Neuronal Properties

Kushnireva,

Segal,

Korkotian

2024

IJMS

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Presenilin 1 (PS1) is a transmembrane proteolytic subunit of γ-secretase that cleaves amyloid precursor proteins. Mutations in PS1 (mPS1) are associated with early-onset familial Alzheimer’s disease (AD). The link between mutated PS1, mitochondrial calcium regulation, and AD has been studied extensively in different test systems. Despite the wide-ranging role of mPS1 in AD, there is a paucity of information on the link between PS1 and neuronal cell death, a hallmark of AD. In the present study, we employed the selective mitochondrial uncoupler carbonyl cyanide chlorophenylhydrazone (CCCP) and compared the reactivity of mPS1-transfected cultured rat hippocampal neurons with PS1 and control neurons in a situation of impaired mitochondrial functions. CCCP causes a slow rise in cytosolic and mitochondrial calcium in all three groups of neurons, with the mPS1 neurons demonstrating a faster rise. Consequently, mPS1 neurons were depolarized by CCCP and measured with TMRM, a mitochondrial voltage indicator, more than the other two groups. Morphologically, CCCP produced more filopodia in mPS1 neurons than in the other two groups, which were similarly affected by the drug. Finally, mPS1 transfected neurons tended to die from prolonged exposure to CCCP sooner than the other groups, indicating an increase in vulnerability associated with a lower ability to regulate excess cytosolic calcium.

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Section: Discussionmentioning

confidence: 99%

Cultured Rat Hippocampal Neurons Exposed to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Undergo a Rapid, Presenilin-Dependent Change in Neuronal Properties

Kushnireva,

Segal,

Korkotian

2024

IJMS

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“…The neuroprotective effect of tPA on CIRI can be achieved by promoting FUNDC1-dependent mitophagy, which improves mitochondrial function and inhibits apoptosis ( Cai et al, 2021 ). It has been found that promotion of mitochondrial autophagy through PINK/PARKIN-mediated ubiquitination of PA2G4/EBP1 contributes to neuroprotection after CIRI ( Hwang et al, 2024 ).…”

Section: The Role Of Mitophagy In the Pathological Mechanism Of Cereb...mentioning

confidence: 99%

The neuroprotective effect of Chinese herbal medicine for cerebral ischemia reperfusion injury through regulating mitophagy

Chen,

Zhang,

et al. 2024

Front. Pharmacol.

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The incidence of ischemic stroke has been increasing annually with an unfavorable prognosis. Cerebral ischemia reperfusion injury can exacerbate nerve damage. Effective mitochondrial quality control including mitochondrial fission, fusion and autophagy, is crucial for maintaining cellular homeostasis. Several studies have revealed the critical role of mitophagy in Cerebral ischemia reperfusion injury. Cerebral ischemia and hypoxia induce mitophagy, and mitophagy exhibits positive and negative effects in cerebral ischemia reperfusion injury. Studies have shown that Chinese herbal medicine can alleviate Cerebral ischemia reperfusion injury and serve as a neuroprotective agent by inhibiting or promoting mitophagy-mediated pathways. This review focuses on the mitochondrial dynamics and mitophagy-related pathways, as well as the role of mitophagy in ischemia reperfusion injury. Additionally, it discusses the therapeutic potential and benefits of Chinese herbal monomers and decoctions in the treatment of ischemic stroke.

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“…Activation of mitophagy during the process of ischemic stroke reperfusion injury helps clear dysfunctional mitochondria, alleviate oxidative stress, and exert a protective effect. Studies have shown that by regulating the signaling pathways related to mitophagy, it is possible to alleviate neuronal cell damage caused by ischemic stroke reperfusion and thus slow down the progression of stroke ( Zhou et al, 2015 ; Hwang et al, 2023 ). Additionally, ferroptosis, as a novel form of cell death caused by the accumulation of intracellular iron ions, is closely related to the release and accumulation of local iron ions in ischemic stroke reperfusion injury.…”

Section: Introductionmentioning

confidence: 99%

Progress of medicinal plants and their active metabolites in ischemia-reperfusion injury of stroke: a novel therapeutic strategy based on regulation of crosstalk between mitophagy and ferroptosis

Zhang,

Wang,

Jiang

et al. 2024

Front. Pharmacol.

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The death of cells can occur through various pathways, including apoptosis, necroptosis, mitophagy, pyroptosis, endoplasmic reticulum stress, oxidative stress, ferroptosis, cuproptosis, and disulfide-driven necrosis. Increasing evidence suggests that mitophagy and ferroptosis play crucial regulatory roles in the development of stroke. In recent years, the incidence of stroke has been gradually increasing, posing a significant threat to human health. Hemorrhagic stroke accounts for only 15% of all strokes, while ischemic stroke is the predominant type, representing 85% of all stroke cases. Ischemic stroke refers to a clinical syndrome characterized by local ischemic-hypoxic necrosis of brain tissue due to various cerebrovascular disorders, leading to rapid onset of corresponding neurological deficits. Currently, specific therapeutic approaches targeting the pathophysiological mechanisms of ischemic brain tissue injury mainly include intravenous thrombolysis and endovascular intervention. Despite some clinical efficacy, these approaches inevitably lead to ischemia-reperfusion injury. Therefore, exploration of treatment options for ischemic stroke remains a challenging task. In light of this background, advancements in targeted therapy for cerebrovascular diseases through mitophagy and ferroptosis offer a new direction for the treatment of such diseases. In this review, we summarize the progress of mitophagy and ferroptosis in regulating ischemia-reperfusion injury in stroke and emphasize their potential molecular mechanisms in the pathogenesis. Importantly, we systematically elucidate the role of medicinal plants and their active metabolites in targeting mitophagy and ferroptosis in ischemia-reperfusion injury in stroke, providing new insights and perspectives for the clinical development of therapeutic drugs for these diseases.

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PA2G4/EBP1 ubiquitination by PRKN/PARKIN promotes mitophagy protecting neuron death in cerebral ischemia

Cited by 10 publications

References 63 publications

Cultured Rat Hippocampal Neurons Exposed to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Undergo a Rapid, Presenilin-Dependent Change in Neuronal Properties

Cultured Rat Hippocampal Neurons Exposed to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Undergo a Rapid, Presenilin-Dependent Change in Neuronal Properties

The neuroprotective effect of Chinese herbal medicine for cerebral ischemia reperfusion injury through regulating mitophagy

Progress of medicinal plants and their active metabolites in ischemia-reperfusion injury of stroke: a novel therapeutic strategy based on regulation of crosstalk between mitophagy and ferroptosis

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