Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD.
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ABSTRACT:
SUBMITTER: Gupta U
PROVIDER: S-EPMC9809950 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD.
Gupta Urvi U Ghosh Sayan S Wallace Callen T CT Shang Peng P Xin Ying Y Nair Archana Padmanabhan AP Yazdankhah Meysam M Strizhakova Anastasia A Ross Mark A MA Liu Haitao H Hose Stacey S Stepicheva Nadezda A NA Chowdhury Olivia O Nemani Mihir M Maddipatla Vishnu V Grebe Rhonda R Das Manjula M Lathrop Kira L KL Sahel José-Alain JA Zigler J Samuel JS Qian Jiang J Ghosh Arkasubhra A Sergeev Yuri Y Handa James T JT St Croix Claudette M CM Sinha Debasish D
Autophagy 20220426 1
In dry age-related macular degeneration (AMD), LCN2 (lipocalin 2) is upregulated. Whereas LCN2 has been implicated in AMD pathogenesis, the mechanism remains unknown. Here, we report that in retinal pigmented epithelial (RPE) cells, LCN2 regulates macroautophagy/autophagy, in addition to maintaining iron homeostasis. LCN2 binds to ATG4B to form an LCN2-ATG4B-LC3-II complex, thereby regulating ATG4B activity and LC3-II lipidation. Thus, increased LCN2 reduced autophagy flux. Moreover, RPE cells f ...[more]
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