Goup leader: Amélie Bernard, researcher CNRS

Amélie Bernard obtained her PhD in plant biology from the University of Bordeaux in 2011, during which she worked on cuticular lipids. She started studying autophagy during her post-doc in the Klionsky Lab (University of Michigan, 2012-2016). In 2016, she obtained a full position at the CNRS and joined the LBM. In 2020, her project ‘LIP-ATG’ was funded by an ERC starting grant. 

Fundings:

“Results incorporated in the standard have received funding from the European Research Council (ERC) under European Union’s Horizon 2020 research and innovation programme (grant agreement No 852136)”

Group members:

J. Joubes (PU), F. Domergue (CR), S. Pascal (AI), J. Castets (PhD), C. Chambaud (IE), J. Lupette (Post-Doc).

Functional characterization of lipids associated with autophagy in plants 

Autophagy is an intracellular catabolic process which integrates environmental and developmental cues to target, degrade and recycle cell components, ensuring quality control and promoting cell homeostasis and adaptation. As such, autophagy is critical throughout eukaryotic life and notably in plants where it acts as a major adaptive program to support plant survival to multiple stresses including nutrient starvation, drought or pathogen attacks.

Autophagy relies on the formation of specialized membrane vesicles called autophagosome (AP) which engulf, traffic and deliver cargo to the lytic vacuole where it is degraded. The number, nature and size of autophagosomes govern rates of autophagy activity and their formation is finely regulated in time and space to adapt to cellular demands, ensuring developmental and environmental plasticity. Nevertheless, how autophagosomes are formed remain poorly understood.  

Unlike other endomembrane vesicles, APs do not bud from a preexisting compartment. Instead, they form de novothrough a multistep process carried out by a group of dedicated proteins (named ATG proteins) and hinging on intense membrane remodeling events. These start with the de novo assembly of an initial membrane compartment, the phagophore which then expands by the addition of lipids and finally fuses to a complete vesicle. At this time how the phagophore membrane is assembled, how it organizes to promote its unique structure, identity and function and how it evolves to support dynamic remodelling for AP formation remain largely elusive in plants. 

To address these questions, our group explores the contribution of lipids in autophagosome formation. In fact, while the core component of the autophagy machinery, the autophagy-related proteins (ATG) have been well characterized, the nature and functions of lipids composing the AP membranes remain largely unknown in plants. Yet, lipids are key components of biological membranes where the great diversity of their structures, biochemical properties and distribution, dictates functional and structural territories supporting membrane organization and activity. In that context, we postulate that lipids forming the phagophore membrane are fundamental functional contributors of AP formation and the overall ambitions of our group are to reveal which and how lipids regulate AP membranes to go beyond our understanding of the molecular mechanisms of autophagy in plantsFocusing on the model plant Arabidopsis thaliana, we develop projects integrating proteomic/bioinformatic approaches, lipidomics and high-resolution 3D imaging into molecular cell biology to explore how lipids’ nature, dynamics and lateral heterogeneity instruct autophagosome formation.

Key publications:

• Gomez ER, Joubès J, Valentin N, Batoko H, Satiat-Jeunemaître B, Bernard A. Lipids in membrane dynamics during autophagy in plants. J Exp Bot 2018; 69:1287-1299.
• Eapen VV , Waterman DP , Bernard A , Schiffman N , Sayas E , Kamber R, Lemos B, Memisoglu G, Ang J, Mazella A, Chuartzman SG, Loewith R, Schuldiner M, Denic V , Klionsky DJ, Haber, JE. A novel pathway of targeted autophagy is induced by DNA damage in budding yeast. PNAS 2017; 114, E1158-E1167.
• Bernard A*, Jin M*, Xu Z, Klionsky DJ. A large-scale analysis of autophagy related gene expression identifies new regulators of autophagy. Autophagy 2015; 2114-2122.
• Hu G*, McQuiston T*, Bernard A*, Park YD, Qiu J, Vural A, Zhang N, Waterman SR, Blewett NH, Myers TG, Maraia RJ, Kehrl JH, Uzel G, Klionsky DJ, Williamson PR. A conserved mechanism of TOR-dependent RCK-mediated mRNA degradation regulates autophagy. Nature Cell Biology 2015; 17:930-942
• Bernard A, Jin M, González-Rodriguez P, Füllgrabe J, Delorme-Axford E, Backues SK, Joseph B, Klionsky DJ. Rph1/KDM4 mediates nutrient-limitation signaling that leads to the transcriptional induction of autophagy. Current Biology 2015; 25:546-555.