EIF5A is required for autophagy by mediating ATG3 translation. (30th April 2018)

• Record Type: Journal Article
• Authors: Lubas, Michal; Harder, Lea M; Kumsta, Caroline; Tiessen, Imke; Hansen, Malene; Andersen, Jens S; Lund, Anders H; Frankel, Lisa B
• Is Part Of: EMBO reports. Volume 19:Number 6(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-04-30
• Subjects: ATG3 -- autophagy -- eIF5A -- translation; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201846072
• Languages: English
• ISSNs: 1469-221X

Abstract

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. Synopsis: Eukaryotic translation initiation factor 5A (eIF5A) is required for lipidation of ATG8 proteins and autophagosome formation. This results from eIF5A‐mediated translation of the E2‐like ATG3 protein, which contains an amino acid motif causing eIF5A dependency for its efficient translation. A high‐throughput screen identifies eIF5A as a translational requirement of autophagy. eIF5A facilitates autophagosome formation by facilitating translation of ATG3. A tri‐peptide motif in ATG3 causes eIF5A dependency for its efficient translation. Induction of autophagy causes enhanced association of eIF5A with the ribosome. Abstract : eIF5A is required for lipidation of ATG8 proteins and autophagosome formation. This results from eIF5A‐mediated translation of the E2‐like ATG3 protein, which contains an amino acid motif causing eIF5A dependency for its efficient translation.