EIF5A is Required for Autophagy by Mediating ATG3 translation

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2018 May 2

PMID 29712776

Citations 43

Authors

Michal Lubas

Lea M Harder

Caroline Kumsta

Imke Tiessen

Malene Hansen

Jens S Andersen

Anders H Lund

Lisa B Frankel

Affiliations

Soon will be listed here.

Abstract

Autophagy is an essential catabolic process responsible for recycling of intracellular material and preserving cellular fidelity. Key to the autophagy pathway is the ubiquitin-like conjugation system mediating lipidation of Atg8 proteins and their anchoring to autophagosomal membranes. While regulation of autophagy has been characterized at the level of transcription, protein interactions and post-translational modifications, its translational regulation remains elusive. Here we describe a role for the conserved eukaryotic translation initiation factor 5A (eIF5A) in autophagy. Identified from a high-throughput screen, we find that eIF5A is required for lipidation of LC3B and its paralogs and promotes autophagosome formation. This feature is evolutionarily conserved and results from the translation of the E2-like ATG3 protein. Mechanistically, we identify an amino acid motif in ATG3 causing eIF5A dependency for its efficient translation. Our study identifies eIF5A as a key requirement for autophagosome formation and demonstrates the importance of translation in mediating efficient autophagy.

Citing Articles

Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control.

Zhang Q, Han W, Wu R, Deng S, Meng J, Yang Y Cell Discov. 2024; 10(1):94.

PMID: 39251577 PMC: 11383958. DOI: 10.1038/s41421-024-00712-w.

P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance.

Jiang X, Baig A, Palazzo G, Del Pizzo R, Bortecen T, Groessl S Nat Commun. 2024; 15(1):7458.

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The Many Faces of Hypusinated eIF5A: Cell Context-Specific Effects of the Hypusine Circuit and Implications for Human Health.

Nakanishi S, Cleveland J Int J Mol Sci. 2024; 25(15).

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Spermidine is essential for fasting-mediated autophagy and longevity.

Hofer S, Daskalaki I, Bergmann M, Friscic J, Zimmermann A, Mueller M Nat Cell Biol. 2024; 26(9):1571-1584.

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Reduction of spermine synthase enhances autophagy to suppress Tau accumulation.

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