류기준 (경상국립대학교)

한빛사논문

조회145

류기준Ki-jun Ryu

경상국립대학교

Proc. Natl. Acad. Sci. USA, Apr 02 2024, 121 (14) | https://doi.org/10.1073/pnas.2318039121 RCHY1 and OPTN are required for melanophagy, selective autophagy of melanosomes

Ki Won Lee^a,b,1, Ki- jun Ryu^c,1, Minju Kim^b, Seyeon Lim^b, Jisu Kim^b, Jeong Yoon Kim^d, Cheol Hwangbo^b,e, Jiyun Yoo^b,e, Yong-Yeon Cho^f, and Kwang Dong Kim^a,b,e,g,2

^aAnti-aging Bio Cell factory Regional Leading Research Center, Gyeongsang National University, Jinju 52828, South Korea;

^bDivision of Applied Life Science (Brain Korea 21 Four), Gyeongsang National University, Jinju 52828, South Korea;

^cResearch Institute of Life Sciences, Gyeongsang National University, Jinju 52828, South Korea;

^dDepartment of Pharmaceutical Engineering, Gyeongsang National University, Jinju 52725, South Korea;

^eDivision of Life Science, Gyeongsang National University, Jinju 52828, South Korea;

^fCollege of Pharmacy, The Catholic University of Korea, Wonmi-Gu, Bucheon-si, Gyeonggi-Do 14662, South Korea; and

^gPlant Molecular Biology and Biotechnology Research Center, Gyeongsang National University, Jinju 52828, South Korea

¹K.W.L. and K.- j.R. contributed equally to this work.

²To whom correspondence may be addressed. : Kwang Dong Kim

Abstract

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, β-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 β-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. β-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.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-08)
연구진국내 연구진
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