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AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion

Cell migration is a complex behavior involving many energy-expensive biochemical events that iteratively alter cell shape and location. Mitochondria, the principal producers of cellular ATP, are dynamic organelles that fuse, divide, and relocate to respond to cellular metabolic demands. Using ovaria...

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Detalles Bibliográficos
Autores principales: Cunniff, Brian, McKenzie, Andrew J., Heintz, Nicholas H., Howe, Alan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007087/
https://www.ncbi.nlm.nih.gov/pubmed/27385336
http://dx.doi.org/10.1091/mbc.E16-05-0286
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author Cunniff, Brian
McKenzie, Andrew J.
Heintz, Nicholas H.
Howe, Alan K.
author_facet Cunniff, Brian
McKenzie, Andrew J.
Heintz, Nicholas H.
Howe, Alan K.
author_sort Cunniff, Brian
collection PubMed
description Cell migration is a complex behavior involving many energy-expensive biochemical events that iteratively alter cell shape and location. Mitochondria, the principal producers of cellular ATP, are dynamic organelles that fuse, divide, and relocate to respond to cellular metabolic demands. Using ovarian cancer cells as a model, we show that mitochondria actively infiltrate leading edge lamellipodia, thereby increasing local mitochondrial mass and relative ATP concentration and supporting a localized reversal of the Warburg shift toward aerobic glycolysis. This correlates with increased pseudopodial activity of the AMP-activated protein kinase (AMPK), a critically important cellular energy sensor and metabolic regulator. Furthermore, localized pharmacological activation of AMPK increases leading edge mitochondrial flux, ATP content, and cytoskeletal dynamics, whereas optogenetic inhibition of AMPK halts mitochondrial trafficking during both migration and the invasion of three-dimensional extracellular matrix. These observations indicate that AMPK couples local energy demands to subcellular targeting of mitochondria during cell migration and invasion.
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spelling pubmed-50070872016-11-16 AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion Cunniff, Brian McKenzie, Andrew J. Heintz, Nicholas H. Howe, Alan K. Mol Biol Cell Articles Cell migration is a complex behavior involving many energy-expensive biochemical events that iteratively alter cell shape and location. Mitochondria, the principal producers of cellular ATP, are dynamic organelles that fuse, divide, and relocate to respond to cellular metabolic demands. Using ovarian cancer cells as a model, we show that mitochondria actively infiltrate leading edge lamellipodia, thereby increasing local mitochondrial mass and relative ATP concentration and supporting a localized reversal of the Warburg shift toward aerobic glycolysis. This correlates with increased pseudopodial activity of the AMP-activated protein kinase (AMPK), a critically important cellular energy sensor and metabolic regulator. Furthermore, localized pharmacological activation of AMPK increases leading edge mitochondrial flux, ATP content, and cytoskeletal dynamics, whereas optogenetic inhibition of AMPK halts mitochondrial trafficking during both migration and the invasion of three-dimensional extracellular matrix. These observations indicate that AMPK couples local energy demands to subcellular targeting of mitochondria during cell migration and invasion. The American Society for Cell Biology 2016-09-01 /pmc/articles/PMC5007087/ /pubmed/27385336 http://dx.doi.org/10.1091/mbc.E16-05-0286 Text en © 2016 Cunniff, McKenzie, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Cunniff, Brian
McKenzie, Andrew J.
Heintz, Nicholas H.
Howe, Alan K.
AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion
title AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion
title_full AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion
title_fullStr AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion
title_full_unstemmed AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion
title_short AMPK activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion
title_sort ampk activity regulates trafficking of mitochondria to the leading edge during cell migration and matrix invasion
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007087/
https://www.ncbi.nlm.nih.gov/pubmed/27385336
http://dx.doi.org/10.1091/mbc.E16-05-0286
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