Voltage-dependent anion channel 1 oligomerization regulates PANoptosis in retinal ischemia-reperfusion injury
Hao Wan1
Xiaoxia Ban1
Ye He1
Yandi Yang1
Ximin Hu1
Lei Shang2
Xinxing Wan3
Qi Zhang4
Kun Xiong5
1.Department of Human Anatomy and Neurobiology,School of Basic Medical Science,Central South University,Changsha,Hunan Province,China2.Jiangxi Research Institute of Ophthalmology and Visual Sciences,Affiliated Eye Hospital of Nanchang University,Nanchang,Jiangxi Province,China3.Department of Endocrinology,Third Xiangya Hospital,Central South University,Changsha,Hunan Province,China4.Department of Human Anatomy and Neurobiology,School of Basic Medical Science,Central South University,Changsha,Hunan Province,China;Department of Ophthalmology,Stanford University School of Medicine,Palo Alto,CA,USA;Key Laboratory of Emergency and Trauma of Ministry of Education,College of Emergency and Trauma,Hainan Medical University,Haikou,Hainan Province,China5.Department of Human Anatomy and Neurobiology,School of Basic Medical Science,Central South University,Changsha,Hunan Province,China;Key Laboratory of Emergency and Trauma of Ministry of Education,College of Emergency and Trauma,Hainan Medical University,Haikou,Hainan Province,China;Hunan Key Laboratory of Ophthalmology,Changsha,Hunan Province,China
摘要：Ischemia-reperfusion injury is a common pathophysiological mechanism in retinal degeneration.PANoptosis is a newly defined integral form of regulated cell death that combines the key features of pyroptosis,apoptosis,and necroptosis.Oligomerization of mitochondrial voltage-dependent anion channel 1 is an important pathological event in regulating cell death in retinal ischemia-reperfusion injury.However,its role in PANoptosis remains largely unknown.In this study,we demonstrated that voltage-dependent anion channel 1 oligomerization-mediated mitochondrial dysfunction was associated with PANoptosis in retinal ischemia-reperfusion injury.Inhibition of voltage-dependent anion channel 1 oligomerization suppressed mitochondrial dysfunction and PANoptosis in retinal cells subjected to ischemia-reperfusion injury.Mechanistically,mitochondria-derived reactive oxygen species played a central role in the voltage-dependent anion channel 1-mediated regulation of PANoptosis by promoting PANoptosome assembly.Moreover,inhibiting voltage-dependent anion channel 1 oligomerization protected against PANoptosis in the retinas of rats subjected to ischemia-reperfusion injury.Overall,our findings reveal the critical role of voltage-dependent anion channel 1 oligomerization in regulating PANoptosis in retinal ischemia-reperfusion injury,highlighting voltage-dependent anion channel 1 as a promising therapeutic target.
机标关键词：ischemiachannelaniondependentinjuryoligomerizationpanoptosisregulates
论文发表日期：2026-04-30
在线出版日期：2026-03-25（本平台首次上网日期，不代表文献的发表时间）
页数：13( 1652-1664 )
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