Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1782451164142370816 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5007087 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT cunniffbrian ampkactivityregulatestraffickingofmitochondriatotheleadingedgeduringcellmigrationandmatrixinvasion AT mckenzieandrewj ampkactivityregulatestraffickingofmitochondriatotheleadingedgeduringcellmigrationandmatrixinvasion AT heintznicholash ampkactivityregulatestraffickingofmitochondriatotheleadingedgeduringcellmigrationandmatrixinvasion AT howealank ampkactivityregulatestraffickingofmitochondriatotheleadingedgeduringcellmigrationandmatrixinvasion |