NPC1 Deficiency Contributes to Autophagy-Dependent Ferritinophagy in HEI-OC1 Auditory Cells

作者：Lihong Liang, Hongshun Wang, Jun Yao, Qinjun Wei, Yajie Lu, Tianming Wang, Xin Cao · 发表于：Frontiers in Molecular Biosciences · 年份：2022 · DOI：10.3389/fmolb.2022.952608 · 被引用次数：16 · 研究领域：Cancer-related molecular mechanisms research、Inflammasome and immune disorders、Autophagy in Disease and Therapy

Niemann-Pick type C disease (NPCD) is a rare genetic syndrome characterized by cholesterol accumulation in multiple organelles. NPCD is mainly caused by gene deficiency of NPC intracellular cholesterol transporter 1 (NPC1). It has been reported that some of the NPCD patients exhibit clinical features of progressive hearing loss at high frequency and iron disorder, but the underlying relationship is unknown. A recent study has reported that ferroptosis contributes to the impairment of cochlear hair cells that are related to sensory hearing. In this study, we generated NPC1-deficient HEI-OC1 cells to show the effect of NPC1 deficiency on cochlear outer hair cells. We found that NPC1 deficiency enhances autophagy-dependent ferritinophagy to release Fe (II). Our work provides important insights into the effect of NPC1 deficiency in auditory cells, indicating that it induces ferroptosis and results in hearing loss.