Lysosomal Recycling of Amino Acids Affects ER Quality Control

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Jul 9

PMID 32637599

Citations 15

Authors

Ryo Higuchi-Sanabria

Koning Shen

Naame Kelet

Phillip A Frankino

Jenni Durieux

Raz Bar-Ziv

Cierra N Sing

Enrique J Garcia

Stefan Homentcovschi

Melissa Sanchez

Rui Wu

Sarah U Tronnes

Larry Joe

Brant Webster

Alex Ahilon-Jeronimo

Samira Monshietehadi

Sofia Dallarda

Corinne Pender

Liza A Pon

Roberto Zoncu

Andrew Dillin

Affiliations

Soon will be listed here.

Abstract

Recent work has highlighted the fact that lysosomes are a critical signaling hub of metabolic processes, providing fundamental building blocks crucial for anabolic functions. How lysosomal functions affect other cellular compartments is not fully understood. Here, we find that lysosomal recycling of the amino acids lysine and arginine is essential for proper ER quality control through the UPR. Specifically, loss of the lysine and arginine amino acid transporter LAAT-1 results in increased sensitivity to proteotoxic stress in the ER and decreased animal physiology. We find that these LAAT-1-dependent effects are linked to glycine metabolism and transport and that the loss of function of the glycine transporter SKAT-1 also increases sensitivity to ER stress. Direct lysine and arginine supplementation, or glycine supplementation alone, can ameliorate increased ER stress sensitivity found in mutants. These data implicate a crucial role in recycling lysine, arginine, and glycine in communication between the lysosome and ER.

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