RCHY1 and OPTN are required for melanophagy, selective autophagy of melanosomes

• 成果类型: Article
• 署名作者: Lee, Ki Won; Ryu, Ki-jun; Kim, Minju; Lim, Seyeon; Kim, Jisu; Kim, Jeong Yoon; Hwangbo, Cheol; Yoo, Jiyun; Cho, Yong-Yeon; Kim, Kwang Dong
• 署名单位: Gyeongsang National University; Gyeongsang National University; Gyeongsang National University; Gyeongsang National University; Gyeongsang National University; Catholic University of Korea; Gyeongsang National University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13280
• DOI: 10.1073/pnas.2318039121
• 发表日期: 2024-03-25
• 关键词: cargo recognition; molecular-basis; e3 ligase; ubiquitin; phosphorylation; degradation; mitophagy; protein; receptors; promotes

摘要

Melanosomes are specific organelles dedicated to melanin synthesis and accumulation in melanocytes. Autophagy is suggestively involved in melanosome degradation, although the potential underlying molecular mechanisms remain elusive. In selective autophagy, autophagy receptors and E3- ligases are the key factors conferring cargo selectivity. In B16F10 cells, (3- mangostin efficiently induced melanosome degradation without affecting other organelles such as mitochondria, peroxisomes, and the endoplasmic reticulum. Among various autophagy receptors, optineurin (OPTN) contributes TANK- binding kinase 1 (TBK1)- dependently to melanosome degradation and its knockdown inhibited (3- mangostin- mediated melanosome degradation. OPTN translocation to melanosomes was dependent on its ubiquitin- binding domain. Moreover, OPTN- mediated TBK1 activation and subsequent TBK1- mediated S187 OPTN phosphorylation were essential for melanosome degradation. (3- mangostin increased K63- linked melanosome ubiquitination. Finally, the E3- ligase RCHY1 knockdown inhibited the melanosome ubiquitination required for OPTN- and TBK1- phosphorylation as well as melanosome degradation. This study suggests that melanophagy, melanosome- selective autophagy, contributes to melanosome degradation, and OPTN and RCHY1 are an essential autophagy receptor and a E3- ligase, respectively, conferring cargo selectivity in melanophagy.