Monitoring lipophagy in kidney epithelial cells in response to shear stress.

Published on Jan 1, 2021
· DOI :10.1016/BS.MCB.2020.12.003
Federica Roccio1
Estimated H-index: 1
Aurore Claude-Taupin (University of Paris)+ 3 AuthorsNicolas Dupont15
Estimated H-index: 15
(University of Paris)
#1Caterina Miceli (University of Paris)H-Index: 2
#2Federica Roccio (University of Paris)H-Index: 1
Last. Nicolas Dupont (University of Paris)H-Index: 15
view all 13 authors...
Organs and cells must adapt to shear stress induced by biological fluids, but how fluid flow contributes to the execution of specific cell programs is poorly understood. Here we show that shear stress favours mitochondrial biogenesis and metabolic reprogramming to ensure energy production and cellular adaptation in kidney epithelial cells. Shear stress stimulates lipophagy, contributing to the production of fatty acids that provide mitochondrial substrates to generate ATP through β-oxidation. Th...
14 CitationsSource
#1Asma Boukhalfa (Paris V: Paris Descartes University)H-Index: 3
#2Anna Chiara Nascimbeni (Paris V: Paris Descartes University)H-Index: 12
Last. Etienne Morel (Paris V: Paris Descartes University)H-Index: 26
view all 9 authors...
Cells subjected to stress situations mobilize specific membranes and proteins to initiate autophagy. Phosphatidylinositol-3-phosphate (PI3P), a crucial lipid in membrane dynamics, is known to be essential in this context. In addition to nutriments deprivation, autophagy is also triggered by fluid-flow induced shear stress in epithelial cells, and this specific autophagic response depends on primary cilium (PC) signaling and leads to cell size regulation. Here we report that PI3KC2α, required for...
16 CitationsSource
#1Micah B. Schott (Mayo Clinic)H-Index: 9
#2Shaun G. Weller (Mayo Clinic)H-Index: 14
Last. Mark A. McNiven (Mayo Clinic)H-Index: 4
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Lipid droplet (LD) catabolism in hepatocytes is mediated by a combination of lipolysis and a selective autophagic mechanism called lipophagy, but the relative contributions of these seemingly distinct pathways remain unclear. We find that inhibition of lipolysis, lipophagy, or both resulted in similar overall LD content but dramatic differences in LD morphology. Inhibition of the lipolysis enzyme adipose triglyceride lipase (ATGL) resulted in large cytoplasmic LDs, whereas lysosomal inhibition c...
53 CitationsSource
#1Satoshi Minami (Osaka University)H-Index: 8
#2Takeshi Yamamoto (Osaka University)H-Index: 9
Last. Yoshitaka Isaka (Osaka University)H-Index: 64
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ABSTRACTMacroautophagy/autophagy is a self-degradation process that combats starvation. Lipids are the main energy source in kidney proximal tubular cells (PTCs). During starvation, PTCs increase fatty acid (FA) uptake, form intracellular lipid droplets (LDs), and hydrolyze them for use. The involvement of autophagy in lipid metabolism in the kidney remains largely unknown. Here, we investigated the autophagy-mediated regulation of renal lipid metabolism during prolonged starvation using PTC-spe...
26 CitationsSource
Macroautophagy (hereafter called autophagy) is a vacuolar, lysosomal pathway for catabolism of intracellular material that is conserved among eukaryotic cells. Autophagy plays a crucial role in tissue homeostasis, adaptation to stress situations, immune responses, and the regulation of the inflammatory response. Blockade or uncontrolled activation of autophagy is associated with cancer, diabetes, obesity, cardiovascular disease, neurodegenerative disease, autoimmune disease, infection, and chron...
94 CitationsSource
#1Nicolas Dupont (Paris V: Paris Descartes University)H-Index: 15
#2Patrice Codogno (Paris V: Paris Descartes University)H-Index: 91
Autophagy is a fundamental cell biological process that controls the quality and quantity of the eukaryotic cytoplasm. Dysfunctional autophagy, when defective or excessive, has been linked to human pathologies ranging from neurodegenerative and infectious diseases to cancer and inflammatory diseases. Autophagy takes place at basal levels in all eukaryotic cells. The process is stimulated during metabolic, genotoxic, infectious, and hypoxic stress conditions and acts an adaptive mechanism essenti...
9 CitationsSource
#1Shuyan Zhang (CAS: Chinese Academy of Sciences)H-Index: 13
#2Yang Wang (CAS: Chinese Academy of Sciences)H-Index: 18
Last. Pingsheng Liu (CAS: Chinese Academy of Sciences)H-Index: 48
view all 10 authors...
Lipid droplet (LD), a multi-functional organelle, is often found to associate with other cellular membranous structures and vary in size in a given cell, which may be related to their functional diversity. Here we established a method to separate LD subpopulations from isolated CHO K2 LDs into three different size categories. The subpopulation with smallest LDs was nearly free of ER and other membranous structures while those with larger LDs contained intact ER. These distinct subpopulations of ...
51 CitationsSource
#1Idil Orhon (Paris V: Paris Descartes University)H-Index: 3
#2Nicolas Dupont (Paris V: Paris Descartes University)H-Index: 15
Last. Patrice Codogno (Paris V: Paris Descartes University)H-Index: 91
view all 13 authors...
Orhon et al. report that primary-cilium-mediated fluid flow sensing triggers autophagy through LKB1–AMPK–mTOR signalling, and thereby controls the volume of kidney epithelial cells.
80 CitationsSource
#1Tomer Shpilka (Weizmann Institute of Science)H-Index: 12
#2Evelyn Welter (Weizmann Institute of Science)H-Index: 3
Last. Zvulun Elazar (Weizmann Institute of Science)H-Index: 55
view all 7 authors...
Autophagy is a major catabolic process responsible for the delivery of proteins and organelles to the lysosome/vacuole for degradation. Malfunction of this pathway has been implicated in numerous pathological conditions. Different organelles have been found to contribute to the formation of autophagosomes, but the exact mechanism mediating this process remains obscure. Here, we show that lipid droplets (LDs) are important for the regulation of starvation-induced autophagy. Deletion of Dga1 and L...
137 CitationsSource
#1Susmita Kaushik (Albert Einstein College of Medicine)H-Index: 46
#2Ana Maria Cuervo (Albert Einstein College of Medicine)H-Index: 121
Cuervo and colleagues find that perilipin proteins associated with lipid droplets are degraded by chaperone-mediated autophagy to facilitate recruitment of the lipolytic machinery to lipid droplets.
301 CitationsSource
Cited By1
#1Aurore Claude-Taupin (University of Paris)
#2Patrice Codogno (University of Paris)H-Index: 11
Last. Nicolas Dupont (University of Paris)H-Index: 15
view all 3 authors...
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...