ArticleMolecular neurobiology2023
Yap1-Usp14 Axis Inhibits Neuronal Mitophagy During Neonatal Hypoxia-Ischemia Encephalopathy by Regulation of Beclin-1 Ubiquitination in Mouse.
Article in Molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 15 citations in OpenAlex.
- Characterization of a new mitophagy reporter uncovers requirement of BNIP3 for hypoxia-induced mitophagy in Drosophila.Research square · 2026Article
- Mitochondrial dysfunction in neonatal brain injury: from molecular mechanisms to therapeutic interventions.Journal of translational medicine · 2026Review
- O-GlcNAcylation of YAP1 promotes lung transplant ischemia-reperfusion injury via binding to HIF1α transcription factor and activating autophagy and mitophagy.Cell death & disease · 2026Article
- Ubiquitin-specific protease 14 inhibition promotes mitophagy and attenuates neural apoptosis after spinal cord injury.Scientific reports · 2025Article
- Gastrodin Protects Neuronal Cells Against Oxidative Stress Through miRNA-125b-5p/Mamdc2 Axis.Neuromolecular medicine · 2025Article
- A closer look at the role of deubiquitinating enzymes in the Hypoxia Inducible Factor pathway.Biochemical Society transactions · 2024Review
- PHLDA1 contributes to hypoxic ischemic brain injury in neonatal rats via inhibiting FUNDC1-mediated mitophagy.Acta pharmacologica Sinica · 2024Article
- Usp14 deficiency removes α-synuclein by regulating S100A8/A9 in Parkinson's disease.Cellular and molecular life sciences : CMLS · 2024Article
- [Expression and significance of hypoxia-inducible factor 1α and Bcl-2/adenovirus E1B19kDa-interacting protein 3 in children with traumatic brain injury].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Article
- MAM-mediated mitophagy and endoplasmic reticulum stress: the hidden regulators of ischemic stroke.Frontiers in cellular neuroscience · 2024Review
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5 authors at 2 institutions in 1 country.
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Abstract
Neonatal hypoxic-ischemic encephalopathy (HIE) that results from perinatal cerebral hypoxia-ischemia has become one of the leading causes of acute mortality and chronic disability in infants and children. Despite that neuronal mitophagy and subsequent clearance of damaged neurons exert protective effect, the pathogenesis of HIE and effective treatment strategies for intervention of HIE remain poorly understood. Here, we report that ubiquitin-specific protease 14 (Usp14, a deubiquitinating enzyme) is closely associated with HIE progression by its negative regulation in neuronal mitophagy in mouse. The expression of Usp14 is elevated in both an oxygen-glucose deprivation (OGD) mouse neuronal cell line culture model in vitro and a HIE mouse model in vivo. Mechanistically, OGD treatment activates Hippo signaling that enhances Yap1 phosphorylation levels at Ser-127 but inhibits Yap1 protein level, which potentiates Usp14 transcription and leads to the downregulated ubiquitination at Lys-63 of Beclin-1, a key molecule in autophagy, resulting in the suppressed neuronal mitophagy, subsequent failure in the clearance of damaged neurons, and finally possible dysregulation in brain functions. Thus, our results provide with Usp14 as a novel target and treatment strategy for intervention of HIE, which may help diagnose and treat HIE in clinic.
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