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Article ; Online: To squeeze or not: Regulation of cell size by mechanical forces in development and human diseases.

Claude-Taupin, Aurore / Dupont, Nicolas

2023 Volume 116, Issue 2, Page(s) e2200101

Abstract: Physical constraints, such as compression, shear stress, stretching and tension play major roles during development and tissue homeostasis. Mechanics directly impact physiology, and their alteration is also recognized as having an active role in driving ... ...

Abstract	Physical constraints, such as compression, shear stress, stretching and tension play major roles during development and tissue homeostasis. Mechanics directly impact physiology, and their alteration is also recognized as having an active role in driving human diseases. Recently, growing evidence has accumulated on how mechanical forces are translated into a wide panel of biological responses, including metabolism and changes in cell morphology. The aim of this review is to summarize and discuss our knowledge on the impact of mechanical forces on cell size regulation. Other biological consequences of mechanical forces will not be covered by this review. Moreover, wherever possible, we also discuss mechanosensors and molecular and cellular signaling pathways upstream of cell size regulation. We finally highlight the relevance of mechanical forces acting on cell size in physiology and human diseases.
MeSH term(s)	Humans ; Stress, Mechanical ; Cell Size ; Mechanotransduction, Cellular/physiology
Language	English
Publishing date	2023-12-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	245745-3
ISSN	1768-322X ; 0399-0311 ; 0248-4900
ISSN (online)	1768-322X
ISSN	0399-0311 ; 0248-4900
DOI	10.1111/boc.202200101
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Article ; Online: A historical perspective of macroautophagy regulation by biochemical and biomechanical stimuli

Dupont, Nicolas / Claude‐Taupin, Aurore / Codogno, Patrice

FEBS Letters. 2024 Jan., v. 598, no. 1 p.17-31

2024

Abstract: Macroautophagy is a lysosomal degradative pathway for intracellular macromolecules, protein aggregates, and organelles. The formation of the autophagosome, a double membrane‐bound structure that sequesters cargoes before their delivery to the lysosome, ... ...

Abstract	Macroautophagy is a lysosomal degradative pathway for intracellular macromolecules, protein aggregates, and organelles. The formation of the autophagosome, a double membrane‐bound structure that sequesters cargoes before their delivery to the lysosome, is regulated by several stimuli in multicellular organisms. Pioneering studies in rat liver showed the importance of amino acids, insulin, and glucagon in controlling macroautophagy. Thereafter, many studies have deciphered the signaling pathways downstream of these biochemical stimuli to control autophagosome formation. Two signaling hubs have emerged: the kinase mTOR, in a complex at the surface of lysosomes which is sensitive to nutrients and hormones; and AMPK, which is sensitive to the cellular energetic status. Besides nutritional, hormonal, and energetic fluctuations, many organs have to respond to mechanical forces (compression, stretching, and shear stress). Recent studies have shown the importance of mechanotransduction in controlling macroautophagy. This regulation engages cell surface sensors, such as the primary cilium, in order to translate mechanical stimuli into biological responses.
Keywords	autophagosomes ; biomechanics ; glucagon ; insulin ; liver ; lysosomes ; macroautophagy ; mechanotransduction ; rats ; shear stress
Language	English
Dates of publication	2024-01
Size	p. 17-31.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	REVIEW
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.14744
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Article ; Online: Yapping at the autophagy door? The answer is flowing in the kidney proximal tubule.

Claude-Taupin, Aurore / Terzi, Fabiola / Codogno, Patrice / Dupont, Nicolas

Autophagy

2024 , Page(s) 1–2

Abstract: Shear stress induced by urinary flow stimulates macroautophagy (hereafter referred to as autophagy) in kidney proximal tubule epithelial cells. Autophagy and selective degradation of lipid droplets by lipophagy contribute to tubule homeostasis by the ... ...

Abstract	Shear stress induced by urinary flow stimulates macroautophagy (hereafter referred to as autophagy) in kidney proximal tubule epithelial cells. Autophagy and selective degradation of lipid droplets by lipophagy contribute to tubule homeostasis by the production of ATP and control of epithelial cell size. Autophagy/lipophagy is controlled by a signaling cascade emanating from the primary cilium, localized at the apical side of epithelial cells. Downstream of the primary cilium, AMPK controls mitochondrial biogenesis on the one hand and autophagy/lipophagy on the other hand, which together increase fatty acid production that fuels oxidative phosphorylation to increase energy production. Recently, we reported that the co-transcriptional factors YAP1 and WWTR1/TAZ act downstream of AMPK to control autophagy. In fact, YAP1 and the transcription factor TEAD control the expression of RUBCN/rubicon. Under shear stress, YAP1 is excluded from the nucleus in a SIRT1-dependent manner to favor autophagic flux by downregulating the expression of RUBCN. When simulating
Language	English
Publishing date	2024-02-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2024.2319023
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Article ; Online: A historical perspective of macroautophagy regulation by biochemical and biomechanical stimuli.

Dupont, Nicolas / Claude-Taupin, Aurore / Codogno, Patrice

FEBS letters

2023 Volume 598, Issue 1, Page(s) 17–31

Abstract: Macroautophagy is a lysosomal degradative pathway for intracellular macromolecules, protein aggregates, and organelles. The formation of the autophagosome, a double membrane-bound structure that sequesters cargoes before their delivery to the lysosome, ... ...

Abstract	Macroautophagy is a lysosomal degradative pathway for intracellular macromolecules, protein aggregates, and organelles. The formation of the autophagosome, a double membrane-bound structure that sequesters cargoes before their delivery to the lysosome, is regulated by several stimuli in multicellular organisms. Pioneering studies in rat liver showed the importance of amino acids, insulin, and glucagon in controlling macroautophagy. Thereafter, many studies have deciphered the signaling pathways downstream of these biochemical stimuli to control autophagosome formation. Two signaling hubs have emerged: the kinase mTOR, in a complex at the surface of lysosomes which is sensitive to nutrients and hormones; and AMPK, which is sensitive to the cellular energetic status. Besides nutritional, hormonal, and energetic fluctuations, many organs have to respond to mechanical forces (compression, stretching, and shear stress). Recent studies have shown the importance of mechanotransduction in controlling macroautophagy. This regulation engages cell surface sensors, such as the primary cilium, in order to translate mechanical stimuli into biological responses.
MeSH term(s)	Autophagy/physiology ; Macroautophagy ; Mechanotransduction, Cellular ; Autophagosomes/metabolism ; Phagocytosis ; Lysosomes/metabolism
Language	English
Publishing date	2023-10-15
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1002/1873-3468.14744
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Article: Autophagy and the primary cilium in cell metabolism: What's upstream?

Claude-Taupin, Aurore / Dupont, Nicolas / Codogno, Patrice

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 1046248

Abstract: The maintenance of cellular homeostasis in response to extracellular stimuli, i.e., nutrient and hormone signaling, hypoxia, or mechanical forces by autophagy, is vital for the health of various tissues. The primary cilium (PC) is a microtubule-based ... ...

Abstract	The maintenance of cellular homeostasis in response to extracellular stimuli, i.e., nutrient and hormone signaling, hypoxia, or mechanical forces by autophagy, is vital for the health of various tissues. The primary cilium (PC) is a microtubule-based sensory organelle that regulates the integration of several extracellular stimuli. Over the past decade, an interconnection between autophagy and PC has begun to be revealed. Indeed, the PC regulates autophagy and in turn, a selective form of autophagy called ciliophagy contributes to the regulation of ciliogenesis. Moreover, the PC regulates both mitochondrial biogenesis and lipophagy to produce free fatty acids. These two pathways converge to activate oxidative phosphorylation and produce ATP, which is mandatory for cell metabolism and membrane transport. The autophagy-dependent production of energy is fully efficient when the PC senses shear stress induced by fluid flow. In this review, we discuss the cross-talk between autophagy, the PC and physical forces in the regulation of cell biology and physiology.
Language	English
Publishing date	2022-11-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.1046248
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Article ; Online: Links between autophagy and tissue mechanics.

Claude-Taupin, Aurore / Codogno, Patrice / Dupont, Nicolas

Journal of cell science

2021 Volume 134, Issue 17

Abstract: Physical constraints, such as compression, shear stress, stretching and tension, play major roles during development, tissue homeostasis, immune responses and pathologies. Cells and organelles also face mechanical forces during migration and ... ...

Abstract	Physical constraints, such as compression, shear stress, stretching and tension, play major roles during development, tissue homeostasis, immune responses and pathologies. Cells and organelles also face mechanical forces during migration and extravasation, and investigations into how mechanical forces are translated into a wide panel of biological responses, including changes in cell morphology, membrane transport, metabolism, energy production and gene expression, is a flourishing field. Recent studies demonstrate the role of macroautophagy in the integration of physical constraints. The aim of this Review is to summarize and discuss our knowledge of the role of macroautophagy in controlling a large panel of cell responses, from morphological and metabolic changes, to inflammation and senescence, for the integration of mechanical forces. Moreover, wherever possible, we also discuss the cell surface molecules and structures that sense mechanical forces upstream of macroautophagy.
MeSH term(s)	Autophagy ; Cell Membrane ; Homeostasis ; Immunity ; Stress, Mechanical
Language	English
Publishing date	2021-09-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.258589
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Article ; Online: Primary cilium-dependent autophagy in the response to shear stress.

Morel, Etienne / Dupont, Nicolas / Codogno, Patrice

Biochemical Society transactions

2021 Volume 49, Issue 6, Page(s) 2831–2839

Abstract: Mechanical forces, such as compression, shear stress and stretching, play major roles during development, tissue homeostasis and immune processes. These forces are translated into a wide panel of biological responses, ranging from changes in cell ... ...

Abstract	Mechanical forces, such as compression, shear stress and stretching, play major roles during development, tissue homeostasis and immune processes. These forces are translated into a wide panel of biological responses, ranging from changes in cell morphology, membrane transport, metabolism, energy production and gene expression. Recent studies demonstrate the role of autophagy in the integration of these physical constraints. Here we focus on the role of autophagy in the integration of shear stress induced by blood and urine flows in the circulatory system and the kidney, respectively. Many studies highlight the involvement of the primary cilium, a microtubule-based antenna present at the surface of many cell types, in the integration of extracellular stimuli. The cross-talk between the molecular machinery of autophagy and that of the primary cilium in the context of shear stress is revealed to be an important dialog in cell biology.
MeSH term(s)	Autophagy/physiology ; Cilia/physiology ; Stress, Mechanical
Language	English
Publishing date	2021-11-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	184237-7
ISSN	1470-8752 ; 0300-5127
ISSN (online)	1470-8752
ISSN	0300-5127
DOI	10.1042/BST20210810
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Article ; Online: La lipide-kinase cachée derrière le PI3P - Dialogue entre cil primaire et machinerie autophagique.

Codogno, Patrice / Dupont, Nicolas / Morel, Étienne

Medecine sciences : M/S

2021 Volume 37, Issue 1, Page(s) 9–11

Title translation	The lipid kinase hidden behind the PI3P: a specific dialogue between the primary cilium and autophagic machinery.
MeSH term(s)	Animals ; Autophagosomes/physiology ; Autophagy/physiology ; Autophagy-Related Protein 8 Family/metabolism ; Autophagy-Related Proteins/metabolism ; Cilia/metabolism ; Class I Phosphatidylinositol 3-Kinases/metabolism ; Class III Phosphatidylinositol 3-Kinases/genetics ; Class III Phosphatidylinositol 3-Kinases/metabolism ; Epithelial Cells/physiology ; Membrane Proteins/metabolism ; Mice ; Microtubule-Associated Proteins/metabolism ; Phosphate-Binding Proteins/metabolism ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol Phosphates/metabolism ; rab GTP-Binding Proteins/metabolism
Chemical Substances	ATG16L1 protein, human ; Autophagy-Related Protein 8 Family ; Autophagy-Related Proteins ; GABARAPL2 protein, human ; MAP1LC3A protein, human ; Membrane Proteins ; Microtubule-Associated Proteins ; Phosphate-Binding Proteins ; Phosphatidylinositol Phosphates ; WIPI2 protein, human ; phosphatidylinositol 3-phosphate ; Class I Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; Class III Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; rab11 protein (EC 3.6.1.-) ; rab GTP-Binding Proteins (EC 3.6.5.2)
Language	French
Publishing date	2021-01-25
Publishing country	France
Document type	News
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/2020248
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Article ; Online: The autophagy protein ATG16L1 cooperates with IFT20 and INPP5E to regulate the turnover of phosphoinositides at the primary cilium.

Boukhalfa, Asma / Roccio, Federica / Dupont, Nicolas / Codogno, Patrice / Morel, Etienne

Cell reports

2021 Volume 35, Issue 4, Page(s) 109045

Abstract: The primary cilium (PC) regulates signalization linked to external stress sensing. Previous works established a functional interplay between the PC and the autophagic machinery. When ciliogenesis is promoted by serum deprivation, the autophagy protein ... ...

Abstract	The primary cilium (PC) regulates signalization linked to external stress sensing. Previous works established a functional interplay between the PC and the autophagic machinery. When ciliogenesis is promoted by serum deprivation, the autophagy protein ATG16L1 and the ciliary protein IFT20 are co-transported to the PC. Here, we demonstrate that IFT20 and ATG16L1 are part of the same complex requiring the WD40 domain of ATG16L1 and a Y-E-F-I motif in IFT20. We show that ATG16L1-deficient cells exhibit aberrant ciliary structures, which accumulate PI4,5P2, whereas PI4P, a lipid normally concentrated in the PC, is absent. Finally, we demonstrate that INPP5E, a phosphoinositide-associated phosphatase responsible for PI4P generation, interacts with ATG16L1 and that a perturbation of the ATG16L1/IFT20 complex alters its trafficking to the PC. Altogether, our results reveal a function of ATG16L1 in ciliary lipid and protein trafficking, thus directly contributing to proper PC dynamics and functions.
MeSH term(s)	Autophagy/physiology ; Autophagy-Related Proteins/metabolism ; Carrier Proteins/metabolism ; Cilia/metabolism ; Humans ; Phosphatidylinositols/metabolism
Chemical Substances	ATG16L1 protein, human ; Autophagy-Related Proteins ; Carrier Proteins ; IFT20 protein, human ; Phosphatidylinositols
Language	English
Publishing date	2021-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109045
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Article ; Online: When the autophagy protein ATG16L1 met the ciliary protein IFT20.

Boukhalfa, Asma / Roccio, Federica / Dupont, Nicolas / Codogno, Patrice / Morel, Etienne

Autophagy

2021 Volume 17, Issue 7, Page(s) 1791–1793

Abstract: The primary cilium (PC), a plasma membrane microtubule-based structure, is a sensor of extracellular chemical and mechanical stress stimuli. Upon ciliogenesis, the autophagy protein ATG16L1 and the ciliary protein IFT20 are co-transported to the PC. We ... ...

Abstract	The primary cilium (PC), a plasma membrane microtubule-based structure, is a sensor of extracellular chemical and mechanical stress stimuli. Upon ciliogenesis, the autophagy protein ATG16L1 and the ciliary protein IFT20 are co-transported to the PC. We demonstrated in a recent study that IFT20 and ATG16L1 interact in a multiprotein complex. This interaction is mediated by the ATG16L1 WD40 domain and an ATG16L1-binding motif newly identified in IFT20. ATG16L1-deficient cells are decorated by giant ciliary structures hallmarked by defects in PC-associated signaling. These structures uncommonly accumulate phosphatidylinositol-4,5-bisphosphate (PtdIns[4,5]P
MeSH term(s)	Autophagy ; Cilia ; Phosphoric Monoester Hydrolases ; Proteins
Chemical Substances	Proteins ; Phosphoric Monoester Hydrolases (EC 3.1.3.2) ; phosphoinositide 5-phosphatase (EC 3.1.3.36)
Language	English
Publishing date	2021-05-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2021.1935004
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