ArticleFEBS open bio2021
Activation of ERK-Drp1 signaling promotes hypoxia-induced Aβ accumulation by upregulating mitochondrial fission and BACE1 activity.
Article in FEBS open bio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Platelet Drp1 phosphorylation provides a platform for immune-based platelet function testing.Blood · 2026Article
- Signaling Pathways Triggering Therapeutical Potential of Marine-Derived Polysaccharides in Alzheimer's Disease: A Recent Review.Molecular neurobiology · 2026Review
- Decoding GPCR signaling in living cells to advance early therapeutic discovery for neurological disorders.Frontiers in molecular neuroscience · 2026Review
- Glutamine alleviates immunosuppression in polymicrobial sepsis by augmenting bacterial phagocytosis through sustaining the GFAT-DRP1 dependent mitochondrial calcium dynamics.Clinical science (London, England : 1979) · 2025Article
- Natural Small-Molecule Bergapten Ameliorates Amyloid-β Pathology and Neuroinflammation in Alzheimer's Disease.Nutrients · 2025Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Loss of Drosophila ribosomal protein S6 kinase II causes mitochondrial dysfunction and cell death.Disease models & mechanisms · 2025Article
- Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Mitochondrial dysfunction is a hallmark of woody breast myopathy in broiler chickens.Frontiers in physiology · 2025Article
- SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.Journal of translational medicine · 2024Article
- Systemic phospho-defective and phospho-mimetic Drp1 mice exhibit normal growth and development with altered anxiety-like behavior.iScience · 2024Article
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Inflammatory signaling pathways in the treatment of Alzheimer's disease with inhibitors, natural products and metabolites (Review).International journal of molecular medicine · 2023Review
- Mechanisms of Modulation of Mitochondrial Architecture.Biomolecules · 2023Review
- Altered Mitochondrial Morphology and Bioenergetics in a New Yeast Model Expressing Aβ42.International journal of molecular sciences · 2023Article
- Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets.Frontiers in physiology · 2023Review
- Amyloid Beta in Aging and Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Mdivi-1: a promising drug and its underlying mechanisms in the treatment of neurodegenerative diseases.Histology and histopathology · 2022Review
- Mitochondrial Quality Control Strategies: Potential Therapeutic Targets for Neurodegenerative Diseases?Frontiers in neuroscience · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is a risk factor for Alzheimer's disease (AD). Besides, mitochondrial fission is increased in response to hypoxia. In this study, we sought to investigate whether hypoxia-induced mitochondrial fission plays a critical role in regulating amyloid-β (Aβ) production. Hypoxia significantly activated extracellular signal-regulated kinase (ERK), increased phosphorylation of dynamin-related protein 1 (Drp1) at serine 616, and decreased phosphorylation of Drp1 at serine 637. Importantly, hypoxia triggered mitochondrial dysfunction, elevated β-secretase 1 (BACE1) and γ-secretase activities, and promoted Aβ accumulation in HEK293 cells transfected with β-amyloid precursor protein (APP) plasmid harboring the Swedish and Indiana familial Alzheimer's disease mutations (APPSwe/Ind HEK293 cells). Then, we investigated whether the ERK inhibitor PD325901 and Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1) would attenuate hypoxia-induced mitochondrial fission and Aβ generation in APPSwe/Ind HEK293 cells. PD325901 and Mdivi-1 inhibited phosphorylation of Drp1 at serine 616, resulting in reduced mitochondrial fission under hypoxia. Furthermore, hypoxia-induced mitochondrial dysfunction, BACE1 activation, and Aβ accumulation were downregulated by PD325901 and Mdivi-1. Our data demonstrate that hypoxia induces mitochondrial fission, impairs mitochondrial function, and facilitates Aβ generation. The ERK-Drp1 signaling pathway is partly involved in the hypoxia-induced Aβ generation by regulating mitochondrial fission and BACE1 activity. Therefore, inhibition of hypoxia-induced mitochondrial fission may prevent or slow the progression of AD.
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