Ceramide enhances binding of LC3/GABARAP autophagy proteins to cardiolipin-containing membranes.

Autor: Varela YR; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, Leioa E-48940, Spain; Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa E-48940, Spain., Iriondo MN; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, Leioa E-48940, Spain; Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa E-48940, Spain., Etxaniz A; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, Leioa E-48940, Spain; Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa E-48940, Spain., Ballesteros U; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, Leioa E-48940, Spain; Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa E-48940, Spain., Montes LR; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, Leioa E-48940, Spain; Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa E-48940, Spain., Goñi FM; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, Leioa E-48940, Spain; Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa E-48940, Spain., Alonso A; Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, Leioa E-48940, Spain; Department of Biochemistry and Molecular Biology, University of the Basque Country, Leioa E-48940, Spain. Electronic address: alicia.alonso@ehu.eus.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2022 Sep 30; Vol. 217, pp. 748-760. Date of Electronic Publication: 2022 Jul 15.
DOI: 10.1016/j.ijbiomac.2022.07.032
Abstrakt: Macroautophagy, or autophagy, is a process in which cell macromolecules, or even organelles, are engulfed in a double-membrane vesicle, the autophagosome, and directed to a lysosome. Among autophagy-related proteins, LC3/GABARAP constitute a protein family derived from yeast Atg8. They play important roles in autophagosome formation, binding future cargo organelles and promoting autophagosome growth. The involvement of specific lipids in this process is poorly understood. The present study explores the interaction of LC3/GABARAP proteins with phospholipid monolayers and bilayers based on phosphatidylcholine or on sphingomyelin. Cardiolipin is found to be essential for the protein interaction with such bilayers, as measured through gradient centrifugation experiments, while 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. Although in further autophagy steps the LC3/GABARAP proteins are covalently bound to a phospholipid, this is not the case in our system, thus it is proposed that the observed ceramide effects would correspond to very early stages in the process, such as cargo recognition.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: