LC3/GABARAP binding to fluid membranes is potentiated by ceramide

Autophagy. 2023 Apr;19(4):1371-1373. doi: 10.1080/15548627.2022.2136821. Epub 2022 Nov 2.

Abstract

LC3/GABARAP constitute a macroautophagy/autophagy-related protein family derived from yeast Atg8. The involvement of specific lipids in LC3/GABARAP function is poorly understood. Exploring the interaction of LC3/GABARAP proteins with phosphatidylcholine- or sphingomyelin-based bilayers has revealed that cardiolipin is essential for the protein-bilayer interaction, and that ceramide markedly increases binding. Giant unilamellar vesicles examined under confocal fluorescence microscopy reveal that ceramide segregates laterally into very rigid domains, while GABARAP binds only the more fluid regions, suggesting that the enhancing role of ceramide is exerted by the minority of ceramide molecules dispersed in the fluid phase.Abbreviations: Atg8: autophagy-related 8; Cer: ceramide; CL: cardiolipin; eCer: egg ceramide; GABARAP: gamma-aminobutyric acid receptor associated protein; GUV: giant unilamellar vesicle; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; Rho-PE: lissamine rhodamine phosphatidylethanolamine; SM: sphingomyelin.

Keywords: Autophagy proteins; LC3/GABARAP; cardiolipin; ceramide; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy*
  • Autophagy-Related Protein 8 Family / metabolism
  • Cardiolipins
  • Ceramides
  • Microtubule-Associated Proteins* / metabolism
  • Sphingomyelins

Substances

  • Microtubule-Associated Proteins
  • Ceramides
  • Sphingomyelins
  • Cardiolipins
  • Autophagy-Related Protein 8 Family

Grants and funding

This work was supported in part by the Spanish Ministerio de Ciencia e Innovación (MCI), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (grants No. PGC2018-099857-B-I00 and No. PID2021-124461NB-I00), by the Basque Government (grants No. IT1625-22 and IT1270-19), by Fundación Ramón Areces. (CIVP20A6619) by Fundación Biofísica Bizkaia, and by the Basque Excellence Research Centre (BERC) program of the Basque Government. Y.R.V. was a recipient of a pre-doctoral FPU fellowship from the Spanish Ministry of Science, Innovation and Universities (FPU18/00799).