A short isoform of ATG7 fails to lipidate LC3/GABARAP

M H Ogmundsdottir,H M Ogmundsdottir,C Bindesbøll,V Pogenberg,V Fock,L Sooman,E Steingrimsson,R Dilshat,A Simonsen,M Wilmanns

doi:10.1038/s41598-018-32694-7

M H Ogmundsdottir, H M Ogmundsdottir + Show 8 more

Open Access

https://doi.org/10.1038/s41598-018-32694-7

Copy DOI

Abstract

Autophagy is a degradation pathway important for cellular homeostasis. The E1-like enzyme ATG7 is a key component of the autophagy machinery, with the main function of mediating the lipidation of LC3/GABARAP during autophagosome formation. By analysing mRNA-sequencing data we found that in addition to the full-length ATG7 isoform, various tissues express a shorter isoform lacking an exon of 27 amino acids in the C-terminal part of the protein, termed ATG7(2). We further show that ATG7(2) does not bind LC3B and fails to mediate the lipidation of members of the LC3/GABARAP family. We have thus identified an isoform of ATG7 that is unable to carry out the best characterized function of the protein during the autophagic response. This short isoform will have to be taken into consideration when further studying the role of ATG7.

Highlights

IntroductionThe E1-like enzyme ATG7 is a key component of the autophagy machinery, with the main function of mediating the lipidation of LC3/ GABARAP during autophagosome formation
Autophagy is a degradation pathway important for cellular homeostasis
We analysed the expression of ATG7 isoforms utilizing RNA-sequencing data from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases (Fig. 1B)

Summary

Introduction

The E1-like enzyme ATG7 is a key component of the autophagy machinery, with the main function of mediating the lipidation of LC3/ GABARAP during autophagosome formation. We have identified an isoform of ATG7 that is unable to carry out the best characterized function of the protein during the autophagic response This short isoform will have to be taken into consideration when further studying the role of ATG7. Autophagy is a highly conserved clearance pathway of cytoplasmic constituents and is essential for sustaining cellular homeostasis[1] During this catabolic process, cellular components such as protein aggregates, lipids or damaged organelles are delivered to lysosomes, where they become degraded and recycled into building blocks for new cellular constituents and for ATP production[2]. We have identified an isoform of ATG7 that fails to mediate the lipidation of LC3/GABARAP

Methods

Results

Conclusion