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The missing link: how do membrane lipids interplay with ATG proteins to instruct plant autophagy

Project description

Membrane lipids in the autophagy process in plants

Autophagy is a natural mechanism by which cells remove their own dysfunctional components via degradation and recycling. The process requires formation of vesicles called autophagosomes, which engulf intracellular components and deliver them to a lytic vacuole. Autophagosome formation is driven by a dedicated machinery of proteins and lipids. This EU-funded project investigates the less studied fundamental mechanisms of lipids’ contribution in this whole process in plant cells. Research will focus on the fundamental questions exploring how lipids’ nature, dynamics and lateral heterogeneity determines the phagophore structure, its protein composition and functions, using a combination of proteomic/bioinformatic approaches, lipidomics and high-resolution 3D imaging.

Objective

Autophagy is an intracellular catabolic process critical to eukaryotic life and indispensable for plant survival to drought, nutrient scarcity or pathogen attacks. Autophagy relies on the formation of specialized vesicles called autophagosomes (AP) which engulf and deliver cell components to the lytic vacuole. AP biogenesis is carried out by a group of dedicated proteins (named ATG) and hinges on intense remodelling events and on the remarkable capacity of an initial membrane, the phagophore, to assemble de novo, shape like a cup, expand while maintaining structure and function and re-shape to a complete vesicle. To date the molecular mechanisms underlying these events remain elusive. Research has focused on the role of autophagy proteins but, despite AP biogenesis being a membrane-based process, the fundamental contributions of lipids to AP membrane formation, identity and activities have been largely unexplored; in other words, when it comes to AP formation we are only looking at half of the picture.

I propose to address the fundamental question of how APs form and shape from a novel angle: by exploring how lipids’ nature, dynamics and lateral heterogeneity instruct the phagophore structure, its protein composition and its functions. The project builds on our recent results and expands on strategies that we have developed, integrating proteomic/bioinformatic approaches, lipidomics and high-resolution 3D imaging. We will tackle 3 complementary objectives: 1) Reveal the dynamic lipid signature of the phagophore, 2) Elucidate the implication of lipids nature and repartition in the phagophore ultrastructure, 3) Decrypt the molecular mechanisms by which lipids interplay with ATG proteins to control autophagy activity and plant physiology. Overall the project will articulate an integrated vision of the molecular processes controlling autophagy and provide fundamental knowledge in our understanding of plant adaptive programs.

Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution
€ 1 499 880,00
Address
RUE MICHEL ANGE 3
75794 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
€ 1 499 880,00

Beneficiaries (1)