ARMS-NF-κB signaling regulates intracellular ROS to induce autophagy-associated cell death upon oxidative stress

Yi-Hua Liao; June-Tai Wu; I-Chun Hsieh; Hsiu-Hsiang Lee; Pei-Hsin Huang

doi:10.1016/j.isci.2023.106005

ARMS-NF-κB signaling regulates intracellular ROS to induce autophagy-associated cell death upon oxidative stress

iScience. 2023 Jan 18;26(2):106005. doi: 10.1016/j.isci.2023.106005. eCollection 2023 Feb 17.

Authors

Yi-Hua Liao^{1

2}, June-Tai Wu¹, I-Chun Hsieh², Hsiu-Hsiang Lee³, Pei-Hsin Huang^{2

4}

Affiliations

¹ Department of Dermatology, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei 100, Taiwan.
² Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
³ Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
⁴ Department of Pathology, National Taiwan University Hospital, Taipei 100, Taiwan.

Abstract

Ankyrin repeat-rich membrane spanning (ARMS) plays roles in neural development, neuropathies, and tumor formation. Such pleiotropic function of ARMS is often attributed to diverse ARMS-interacting molecules in different cell context. However, it might be achieved by ARMS' effect on global biological mediator like reactive oxygen species (ROS). We established ARMS-knockdown in melanoma cells (siARMS) and in Drosophila eyes (GMR>dARMS ^RNAi ) and challenged them with H₂O₂. Decreased ARMS in both systems compromises nuclear translocation of NF-κB and induces ROS, which in turn augments autophagy flux and confers susceptibility to H₂O₂-triggered autophagic cell death. Resuming NF-κB activity or reducing ROS by antioxidants in siARMS cells and GMR>dARMS ^RNAi fly decreases intracellular peroxides level concurrent with reduced autophagy and attenuated cell death. Conversely, blocking NF-κB activity in wild-type flies/melanoma enhances ROS and induces autophagy with cell death. We thus uncover intracellular ROS modulated by ARMS-NFκB signaling primes autophagy for autophagic cell death upon oxidative stress.

Keywords: Biological sciences; Cell biology; Molecular biology.