Seigo Terawaki
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Molecular and Genetic Medicine,
   Position   Assistant Professor with Special Assignment
Article types 原著
Language English
Peer review Peer reviewed
Title PACSIN1 is indispensable for amphisome-lysosome fusion during basal autophagy and subsets of selective autophagy.
Journal Formal name：PLoS genetics
Abbreviation：PLoS Genet
ISSN code：15537404/15537390
Domestic / ForeginForegin
Volume, Issue, Page 18(6),pp.e1010264
Author and coauthor Oe Yukako, Kakuda Keita, Yoshimura Shin-Ichiro, Hara Naohiro, Hasegawa Junya, Terawaki Seigo, Kimura Yasuyoshi, Ikenaka Kensuke, Suetsugu Shiro, Mochizuki Hideki, Yoshimori Tamotsu, Nakamura Shuhei
Publication date 2022/06
Summary Autophagy is an indispensable process that degrades cytoplasmic materials to maintain cellular homeostasis. During autophagy, double-membrane autophagosomes surround cytoplasmic materials and either fuse with endosomes (called amphisomes) and then lysosomes, or directly fuse with lysosomes, in both cases generating autolysosomes that degrade their contents by lysosomal hydrolases. However, it remains unclear if there are specific mechanisms and/or conditions which distinguish these alternate routes. Here, we identified PACSIN1 as a novel autophagy regulator. PACSIN1 deletion markedly decreased autophagic activity under basal nutrient-rich conditions but not starvation conditions, and led to amphisome accumulation as demonstrated by electron microscopic and co-localization analysis, indicating inhibition of lysosome fusion. PACSIN1 interacted with SNAP29, an autophagic SNARE, and was required for proper assembly of the STX17 and YKT6 complexes. Moreover, PACSIN1 was required for lysophagy, aggrephagy but not mitophagy, suggesting cargo-specific fusion mechanisms. In C. elegans, deletion of sdpn-1, a homolog of PACSINs, inhibited basal autophagy and impaired clearance of aggregated protein, implying a conserved role of PACSIN1. Taken together, our results demonstrate the amphisome-lysosome fusion process is preferentially regulated in response to nutrient state and stress, and PACSIN1 is a key to specificity during autophagy.
DOI 10.1371/journal.pgen.1010264
PMID 35771772