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Mechanical regulation of glycolysis via cytoskeleton architecture

Nature (London), 2020-02, Vol.578 (7796), p.621-626 [Peer Reviewed Journal]

COPYRIGHT 2020 Nature Publishing Group ;COPYRIGHT 2020 Nature Publishing Group ;Copyright Nature Publishing Group Feb 27, 2020 ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/s41586-020-1998-1 ;PMID: 32051585

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Title:
Mechanical regulation of glycolysis via cytoskeleton architecture
Author: Park, Jin Suk ; Burckhardt, Christoph J ; Lazcano, Rossana ; Solis, Luisa M ; Isogai, Tadamoto ; Li, Linqing ; Chen, Christopher S ; Gao, Boning ; Minna, John D ; Bachoo, Robert ; DeBerardinis, Ralph J ; Danuser, Gaudenz
Subjects: Actins - metabolism ; Actomyosin ; Actomyosin - metabolism ; Adhesion ; Animals ; Apoptosis ; Bronchi - cytology ; Cattle ; Cell Differentiation ; Cell Line ; Cell survival ; Cellular Microenvironment ; Contractility ; Cytoskeleton ; Cytoskeleton - metabolism ; Degradation ; Environmental changes ; Enzymes ; Epithelial cells ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; Extracellular matrix ; Gene expression ; Glucose - metabolism ; Glycolysis ; Hardness ; Humans ; Kinases ; Lung cancer ; Lung diseases ; Mechanical properties ; Mechanics ; Mechanics (physics) ; Metabolism ; Metabolites ; Microenvironments ; Morphogenesis ; Myosin ; Neoplasms - metabolism ; Neoplasms - pathology ; Observations ; Phosphofructokinase ; Phosphofructokinases - chemistry ; Phosphofructokinases - metabolism ; Phosphorylation ; Physiological aspects ; Proteasome Endopeptidase Complex - metabolism ; Proteasomes ; Ribonucleoproteins - metabolism ; Sequestering ; Small cell lung carcinoma ; Stiffness ; Stress Fibers - metabolism ; Substrates ; Tumors ; Ubiquitin ; Ubiquitin-protein ligase ; Ubiquitin-Protein Ligases - metabolism
Is Part Of: Nature (London), 2020-02, Vol.578 (7796), p.621-626
Description: The mechanics of the cellular microenvironment continuously modulates cell functions such as growth, survival, apoptosis, differentiation and morphogenesis via cytoskeletal remodelling and actomyosin contractility . Although all of these processes consume energy , it is unknown whether and how cells adapt their metabolic activity to variable mechanical cues. Here we report that the transfer of human bronchial epithelial cells from stiff to soft substrates causes a downregulation of glycolysis via proteasomal degradation of the rate-limiting metabolic enzyme phosphofructokinase (PFK). PFK degradation is triggered by the disassembly of stress fibres, which releases the PFK-targeting E3 ubiquitin ligase tripartite motif (TRIM)-containing protein 21 (TRIM21). Transformed non-small-cell lung cancer cells, which maintain high glycolytic rates regardless of changing environmental mechanics, retain PFK expression by downregulating TRIM21, and by sequestering residual TRIM21 on a stress-fibre subset that is insensitive to substrate stiffness. Our data reveal a mechanism by which glycolysis responds to architectural features of the actomyosin cytoskeleton, thus coupling cell metabolism to the mechanical properties of the surrounding tissue. These processes enable normal cells to tune energy production in variable microenvironments, whereas the resistance of the cytoskeleton in response to mechanical cues enables the persistence of high glycolytic rates in cancer cells despite constant alterations of the tumour tissue.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 0028-0836
EISSN: 1476-4687
DOI: 10.1038/s41586-020-1998-1
PMID: 32051585
Source: ProQuest One Psychology
AUTh Library subscriptions: ProQuest Central
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Mechanical regulation of glycolysis via cytoskeleton architecture

COPYRIGHT 2020 Nature Publishing Group ;COPYRIGHT 2020 Nature Publishing Group ;Copyright Nature Publishing Group Feb 27, 2020 ;ISSN: 0028-0836 ;EISSN: 1476-4687 ;DOI: 10.1038/s41586-020-1998-1 ;PMID: 32051585

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