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Updated: Jul 5, 2025

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
Oxidative stress suppresses PHB2-mediated mitophagy in β-cells via the Nrf2/PHB2 pathway
Shan Liu1,2,3,4, Rui Zhang2,4,5, Lan Zhang6
1Department of Endocrinology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Aims/Introduction:
Mitochondrial damage caused by oxidative stress is a main driver of pancreatic β-cell dysfunction in the pathogenesis of type 2 diabetes mellitus. Prohibitin2 (PHB2) is a vital inner mitochondrial membrane protein that participates in mitophagy to remove the damaged mitochondria. This study aimed to investigate the role and mechanisms of PHB2-mediated mitophagy in oxidative stress-induced pancreatic β-cell dysfunction.
Materials And Methods:
PHB2 and mitophagy-related protein expression were analyzed by real-time polymerase chain reaction and western blotting in RINm5F cells treated with H2O2 and islets of diabetic rats. Mitophagy was observed by mitochondrial and lysosome colocalization. RINm5F cells were transfected by phb2 siRNA or overexpression plasmid to explore the role of PHB2 in mitophagy of RINm5F cells. The mechanism of Nrf2 regulating PHB2 was explored by Nrf2 inhibitor and agonist.
Results:
The expression of PHB2, mitophagy related protein PINK1, and Parkin were decreased in RINm5F cells incubated with H2O2 and in islets of diabetic rats. Overexpression of PHB2 protected β-cells from oxidative stress by promoting mitophagy and inhibiting cell apoptosis, whereas transfection with PHB2 siRNA suppressed mitophagy. Furthermore, PHB2-mediated mitophagy induced by oxidative stress was through the Nrf2/PHB2 pathway in β-cells. Antioxidant NAC alleviated oxidative stress injury by promoting PHB2-mediated mitophagy.
Conclusion:
Our study suggested that PHB2-mediated mitophagy can protect β-cells from apoptosis via the Nrf2/PHB2 pathway under oxidative stress. Antioxidants may protect β-cell from oxidative stress by prompting PHB2-mediated mitophagy. PHB2-mediated mitophagy as a potential mechanism takes part in the oxidative stress induced β-cell injury.
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