Institut Necker Enfants Malades

Focus

The main focus of our research team is to understand how mammalian cells mobilize organelles, endomembrane-based signaling platforms and autophagic machinery to adapt to stress situations and external stimuli.

More information / follow us on:
https://www.researchgate.net/lab/Etienne-Morel-Lab-autophagy-pathway-and-intracellular-membrane-dynamics-Etienne-Morel

https://twitter.com/MorelLab4

Introduction

Mammalian intracellular compartments are highly regulated and renewed to ensure the maintaining of proper cell physiology. In this dynamic context, the intracellular degradative autophagy pathway probably takes advantages of – and initiates dialogs with - pre-existing signaling platforms, organelles and endomembranes. Although there is low-level basal activity, autophagy is mostly associated with stress responses and is considered as an acute protective system that ensures cell homeostasis and contributes directly to cell metabolism and energy regulation. Accordingly, autophagy participates in development, immunity and protects against cell modifications related to ageing. Autophagy involves the formation, and subsequent trafficking, of autophagosomes, which arise from the closure of transient cup-shaped double-membrane structure termed phagophore that capture cytoplasmic cargos for a final delivery to lysosomes. Studying the crosstalk of autophagic machinery with other cellular organelles and structures, such as mitochondria, endosomes and primary cilia, will shed light on the importance of endomembranes and signaling platforms cooperation in stress sensing and homeostasis regulation in a wide variety of mammalian cells.

Research objectives

Our project aims at investigating the cellular and molecular mechanisms that regulate autophagic pathway during stress response in cooperation with other endomembranes, in physiological and pathophysiological situations.

3 interconnected axes are currently investigated in my laboratory:

Space and time orchestration of autophagy associated membrane dynamics processes: roles of phosphoinositides and lipid-kinases, scaffolding proteins, cytoskeleton and membrane contact sites
Cannonical and non-cannonical functions of autophagic machinery during the crosstalk with the primary cilium
Non-cell autonomous functions of mechanical stress induced autophagy in kidney epithelial cells differentiation and metabolism, in normal and pathological situations

Keywords: autophagic membranes and machinery, chemical, nutritional, infectious and mechanical stresses, primary cilium, endosomes, mitochondria, metabolism, membrane dynamics and contact-sites.

5 main publications

The autophagy protein ATG16L1 cooperates with IFT20 and INPP5E to regulate the turnover of phosphoinositides at the primary cilium
Boukhalfa A, Roccio F, Dupont N, Codogno P and Morel E
Cell Reports 2021 Apr
Chemical targeting of NEET proteins reveals their function in mitochondrial morphodynamics
Molino D*, Pila-Castellanos I*, Marjault HB, Amoedo ND, Kopp K, Rochin L, Karmi O, Sohn YS, Lines L, Hamaï A, Joly S, Radreau P, Vonderscher J, Codogno P, Giordano F, Machin P, Rossignol R, Meldrum E, Arnoult D, Ruggieri A, Nechushtai R, De Chassey B and Morel E
EMBO Reports 2020 Nov
The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells
Miceli C*, Penalva-Mousset L*, Roccio F*, Burtin M, Leroy C, Nemazanyy I, Friedlander G, Morel E, Terzi F, Codogno P and Dupont N
Nature Cell Biology, 2020 Aug
PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress
Boukhalfa A*, Nascimbeni AC*, Ramel D, Dupont N, Hirsch E, Gayral S, Laffargue M#, Codogno P and Morel E
Nature Communications, 2020 Jan
ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis
Nascimbeni AC, Giordano F, Dupont N, Grasso D, Vaccaro MI, Codogno P and Morel E.
EMBO Journal, 2017 May

Five major original publications

Boukhalfa A., Roccio F., Dupont N., Codogno P., Morel E. (2021). The autophagy protein ATG16L1 cooperates with IFT20 and INPP5E to regulate the turnover of phosphoinositides at the primary cilium. Cell Reports. Apr 27;35(4):109045. doi: 10.1016/j.celrep.2021.109045

Molino D., Pila-Castellanos I., Marjault H.B., Amoedo N.D., Kopp K., Rochin L., Karmi O., Sohn Y.S., Lines L., Hamaï A., Joly S., Radreau P., Vonderscher J., Codogno P., Giordano F., Machin P., Rossignol R., Meldrum E., Arnoult D., Ruggieri A., Nechushtai R., De Chassey B., Morel E. (2020). Chemical targeting of NEET proteins reveals their function in mitochondrial morphodynamics. EMBO Reports. Dec 3;21(12):e49019. doi: 10.15252/embr.201949019

Miceli C., Roccio F., Penalva-Mousset L., Burtin M., Leroy C., Nemazanyy I., Friedlander G., Morel E., Terzi F., Codogno P., Dupont N. (2020). The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells. Nature Cell Biology. Sep;22(9):1091-1102. doi: 10.1038/s41556-020-0566-0

Boukhalfa A., Nascimbeni A.C., Ramel D., Dupont N., Hirsch E., Gayral S., Laffargue M., Codogno P., Morel E. (2020). PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress. Nature Communications. Jan 15;11(1):294. doi: 10.1038/s41467-019-14086-1

Nascimbeni A.C., Giordano F., Dupont N., Grasso D., Vaccaro M.I., Codogno P., Morel E. (2017). ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis. EMBO Journal. Jul 14;36(14):2018-2033. doi: 10.15252/embj.201797006

List of publications

2022

Membrane protective role of autophagic machinery during infection of epithelial cells by Candida albicans
Lapaquette P, Ducreux A, Basmaciyan L, Paradis T, Bon F, Bataille A, Winckler P, Hube B, d'Enfert C, Esclatine A, Dubus E, Bringer MA, Morel E and Dalle F
Gut Microbes 2022 Jan

2021

Role of mitochondrial morphodynamics and contact sites in the antiviral response
De Chassey B and Morel E
Médecine/Sciences 2021 Dec

Primary cilium-dependent autophagy in the response to shear stress
Morel E, Dupont N and Codogno P
Biochemistry Society Transactions 2021 Dec

ATG9A protects plasma membrane from programmed and incidental permeabilization
Claude-Taupin A, Jia J, Bhujabal Z, Garfa-Traoré M, Kumar S, Peixoto Duarte da Silva G, Javed R, Gu Y, Allers L, Peters R, Wang F, Jesus da Costa L, Pallikkuth S, Lidke KQ, Mauthe M, Verlhac P, Uchiyama Y, Salemi M, Phinney B, Tooze S.A, Mari M.C, Johansen T, Reggiori F, and Deretic V
Nature Cell Biology 2021 June

When the autophagy protein ATG16L1 met the ciliary protein IFT20
Boukhalfa A, Roccio F, Dupont N, Codogno P and Morel E
Autophagy 2021 May

The autophagy protein ATG16L1 cooperates with IFT20 and INPP5E to regulate the turnover of phosphoinositides at the primary cilium
Boukhalfa A, Roccio F, Dupont N, Codogno P^# and Morel E^#
Cell Reports 2021 Apr

ATG4D is the main ATG8 delipidating enzyme in mammalian cells and protects against cerebellar neurodegeneration
Tamargo-Gómez I, Martínez-García G, Suárez M, Rey V, Fueyo A, Codina-Martínez H, Tomás-Zapico C, Bretones G, M. Caravia X, Morel E, Dupont N, Cabo R, Souquere S, Pierron G, Codogno P, López-Otín C, Fernández A, and Mariño G
Cell Death & Differentiation 2021 Apr

The ménage à trois of autophagy, lipid droplets and liver disease
Filali-Mouncef Y, Hunter C, Roccio F, Zagkou S, Dupont N, Primard C, Proikas-Cezanne T, Reggiori F
Autophagy 2021 Apr

Monitoring lipophagy in kidney epithelial cells in response to shear stress
Roccio F, Claude-Taupin A, Botti J, Morel E, Codogno P and Dupont N
Methods in Cell Biology 2021 March

Mitochondrial morphodynamics alteration induced by influenza virus infection as a new antiviral strategy
Pila-Castellanos I*, Molino D*, McKellar J, Lines L, Da Graca J, Tauziet M, Chanteloup L, IMikaelian, Meyniel-Schicklin L, Codogno P, Vonderscher J, Delevoye C, Moncorgé O, Meldrum E, Goujon C, Morel E^# and De Chassey B^#
PLoS Pathogens 2021 Feb

Phosphoinositides: functions in autophagy-related stress responses
Claude-Taupin A and Morel E
BBA Molecular and Cellular Biology of Lipids 2021 Feb

The lipid kinase hidden behind the PI3P: a specific dialog between the primary cilium and autophagic machinery
Codogno P, Dupont N and Morel E
Medecine/Sciences 2021 Jan

2020

Fluid flow-induced shear stress controls the metabolism of proximal tubule kidney epithelial cells through primary cilium dependent lipophagy and mitochondrial biogenesis
Miceli C*, Roccio F*, Penalva-Mousset L*, Morel E, Codogno P^# and Dupont N^#
Autophagy 2020 Dec

Chemical targeting of NEET proteins reveals their function in mitochondrial morphodynamics
Molino D*, Pila-Castellanos I*, Marjault HB, Amoedo ND, Kopp K, Rochin L, Karmi O, Sohn YS, Lines L, Hamaï A, Joly S, Radreau P, Vonderscher J, Codogno P, Giordano F, Machin P, Rossignol R, Meldrum E, Arnoult D, Ruggieri A, Nechushtai R, De Chassey B^# and Morel E^#
EMBO Reports 2020 Nov

The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation ; of kidney epithelial cells
Miceli C*, Penalva-Mousset L*, Roccio F*, Burtin M, Leroy C, Nemazanyy I, Friedlander G, Morel E, Terzi F, Codogno P^# and Dupont N^#
Nature Cell Biology 2020 Aug

Ultrastructural and dynamic studies of the endosomal compartment in Down syndrome
Botté A, Lainé J, Xicota L, Heiligenstein X, Fontaine G, Kasri A, Rivals I, Goh, P, Faklaris O, Cossec JC, Morel E, Rebillat AS, Nizetic D, Raposo G and Potier MC
Acta Neuropathologica Communications 2020 July

Primary cilium-dependent autophagy drafts PIK3C2A to generate PI3P in response to shear stress
Boukhalfa A*, Nascimbeni AC*, Dupont N, Codogno P and Morel E
Autophagy 2020 June

ER membrane and contact sites dynamics in autophagy regulation and stress response
Morel E
Frontiers in Cell and Developmental Biology 2020 May

PI3KC2α-dependent and VPS34-independent generation of PI3P controls primary cilium-mediated autophagy in response to shear stress
Boukhalfa A*, Nascimbeni AC*, Ramel D, Dupont N, Hirsch E, Gayral S, Laffargue M, Codogno P^# and Morel E^#
Nature Communications 2020 Jan

2019

Interplay between primary cilia, ubiquitin-proteasome system and autophagy
Boukhalfa A*, Miceli C*, Ávalos Y, Morel E and Dupont N
Biochimie 2019 July

The primary cilium protein folliculin is part of the autophagy signalling pathway to regulate epithelial cell size in response to fluid flow
Zemirli N*, Boukhalfa A*, Dupont N, Botti J, Codogno P and Morel E
Cell Stress 2019 Feb

Monitoring of Autophagy and Cell Volume Regulation in Kidney Epithelial Cells in Response to Fluid Shear Stress
Lazari MM, Orhon I, Codogno P, Dupont N.
Methods Mol Biol. 2019

Autophagy is required for memory formation and reverses age-related memory decline
Glatigny M*, Moriceau S*, Ramos-Brossier M*, Nascimbeni AC, Shanley MR, Rivagorda M, Boudarene N, Rousseaud A, Settembre C, Kuperwasser N, Friedlander G, Friedman AK, Morel E, Codogno P and Oury F.
Current Biology 2019 Jan

2018

A novel regulator of autophagosome biogenesis and lipid droplet dynamics
Morel E and Codogno P.
EMBO Reports 2018 Sept

FOXO3a provides a quickstep from autophagy inhibition to apoptosis in cancer therapy
Codogno P and Morel E.
Developmental Cell 2018 Mar

Mitochondrial dynamics in basal and stressful conditions
Zemirli N, Morel E and Molino D.
International Journal of Molecular Science 2018 Feb

Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells
Morel E, Ghezzal S, Lucchi G, Truntzer C, Pais de Barros JP, Simon-Plas F, Demignot S, Mineo C, Shaul PW, Leturque A, Rousset M and Carriere V.
BBA Molecular And Cellular Biology of Lipids 2018 Feb

2017

ER-driven membrane contact sites: evolutionary conserved machineries for stress response and autophagy regulation?
Molino D, Nascimbeni AC, Giordano F, Codogno P and Morel E.
Communicative & Integrative Biology 2017 Dec

To be or not be cell-autonomous? Autophagy says both
Fenouille N, Nascimbeni AC, Botti-Millet J, Dupont N, Morel E and Codogno P
Essays in Biochemistry 2017 Dec

Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow.
Vion AC, Kheloufi M, Hammoutene A, Poisson J, Lasselin J, Devue C, Pic I, Dupont N, Busse J, Stark K, Lafaurie-Janvore J, Barakat AI, Loyer X, Souyri M, Viollet B, Julia P, Tedgui A, Codogno P, Boulanger CM, Rautou PE.
Proc Natl Acad Sci U S A. 2017 Oct

Local detection of PI3P at autophagosome biogenesis membrane platforms
Nascimbeni AC, Codogno P and Morel E.
Autophagy 2017 Sept

Autophagosomal membranes assemble at ER-plasma membrane contact sites
Nascimbeni AC, Codogno P and Morel E.
Molecular and Cellular Oncology 2017 July

Cellular and molecular mechanism for secretory autophagy.
Kimura T, Jia J, Claude-Taupin A, Kumar S, Choi SW, Gu Y, Mudd M, Dupont N, Jiang S, Peters R, Farzam F, Jain A, Lidke KA, Adams CM, Johansen T, Deretic V.
Autophagy. 2017 Jun

ER-plasma membrane contact sites contribute to autophagosome biogenesis ; by regulation of local PI3P synthesis
Nascimbeni AC, Giordano F, Dupont N, Grasso D, Vaccaro MI, Codogno P and Morel E.
EMBO Journal 2017 May

PI3P in the regulation of autophagy membrane dynamics
Nascimbeni AC, Codogno P and Morel E.
FEBS Journal 2017 May

The biogenesis of autophagosome: a new challenge for the cell biologist
Morel E.
Médecine/Sciences 2017 Mar

The journey of the autophagosome through mammalian cell organelles and membranes
Molino D, Zemirli N, Codogno P and Morel E.
Journal of Molecular Biology 2017 Feb

Autophagy: a Druggable Process
Morel E, Mehrpour M, Botti J, Dupont N, Hamaï A, Nascimbeni AC and Codogno P.
Annual Reviews in Pharmacology and Toxicology 2017 Jan

Etienne Morel is an INSERM research director (DR2) and group leader in the cell biology department of INEM. He obtained his PhD degree in Physiology and Cell Biology from Pierre et Marie Curie (Sorbonne) University in 2003 after 3 years as a graduate student in the lab of Jean Chambaz and Monique Rousset where he worked on lipoproteins trafficking and prion infection in epithelial cells. He then specialized on basic aspects of cellular biology by studying endosomal membrane dynamics in the lab of Jean Gruenberg in Geneva (Postdoc #1, 2004-2009, Dept. of Biochemistry of the University of Geneva) as well as in the biology of endosomal phosphoinositides in Alzheimer’s disease in the labs of Gilbert di Paolo and Scott Small in New York (Postdoc #2, 2009-2010, Cell Biology & Pathology Dept. of Columbia University). After having a permanent position at INSERM, he came back to France, at the Centre de Recherche des Cordeliers in Paris where he studied the role of autophagosome in neutral lipids behavior in enterocytes from 2010 to 2013. In 2014 he joined the research group of Patrice Codogno at the cell biology dept. of Institut Necker Enfants Malades to develop projects on basic autophagy in the context of stress sensing and he became group-leader of the “autophagy pathway and intracellular compartments dynamics” lab in 2019. The main goal of his research team is to understand how mammalian cells organelles and intracellular components cooperate with autophagic machinery to respond to stress stimuli. Recent data obtained in the lab identified several signaling platforms and organelles as key regulators of stress sensing and autophagic processes, such as the primary cilium, the mitochondria, the endosomal network or the membrane contact sites.

https://sbcf.fr/member/etienne-morel/