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.

doi:10.1091/mbc.e16-05-0286

Cited by 172 publications

(213 citation statements)

References 75 publications

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“…Transferred FA that fuel FAO may remodel the mitochondrial network in melanoma cells to redistribute these organelles to the cell extremities, which promotes cell migration. The limited data available suggest that the mitochondrial network is reorganized during B16-F10 migration (Cunniff et al, 2016). Although mitochondrial fission is a focus of many studies, both fission and fusion events are critical to redistribute mitochondria toward the leading cell edge during migration (Desai et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…For FAO to efficiently take place in cell protrusions and supply energy for cell migration, we expected that both the mitochondrial machinery and the substrate would be present. Finally, to study the specificity of these processes in response to adipocyte EV, we stimulated cell migration using TNF-a (Appendix Fig S11A) and although this triggered mitochondrial redistribution, as expected (Zhao et al, 2013;Cunniff et al, 2016), TNF-a had no effect on lipid droplet accumulation or redistribution in melanoma cells (Appendix Fig S11B). Obesity further exacerbated this redistribution ( Fig 6B).…”

Section: Melanoma Cells + 3t3-evmentioning

confidence: 91%

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Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

et al. 2020

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Extracellular vesicles are emerging key actors in adipocyte communication. Notably, small extracellular vesicles shed by adipocytes stimulate fatty acid oxidation and migration in melanoma cells and these effects are enhanced in obesity. However, the vesicular actors and cellular processes involved remain largely unknown. Here, we elucidate the mechanisms linking adipocyte extracellular vesicles to metabolic remodeling and cell migration. We show that adipocyte vesicles stimulate melanoma fatty acid oxidation by providing both enzymes and substrates. In obesity, the heightened effect of extracellular vesicles depends on increased transport of fatty acids, not fatty acid oxidation-related enzymes. These fatty acids, stored within lipid droplets in cancer cells, drive fatty acid oxidation upon being released by lipophagy. This increase in mitochondrial activity redistributes mitochondria to membrane protrusions of migrating cells, which is necessary to increase cell migration in the presence of adipocyte vesicles. Our results provide key insights into the role of extracellular vesicles in the metabolic cooperation that takes place between adipocytes and tumors with particular relevance to obesity.

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Section: Discussionmentioning

confidence: 99%

Section: Melanoma Cells + 3t3-evmentioning

confidence: 91%

Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

et al. 2020

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“…As a master regulator of energy homeostasis, AMPK is very likely to target more aspects and functions of mitochondria. For example, AMPK has recently been shown to affect the movement of mitochondria at the leading edge of the cell during cell migration 155 , a process probably involving a yet-to-be-identified substrate of AMPK involved in the process of mitochondrial transport. AKAP1, a mitochondria-localized protein known to act as a PKA-anchoring factor, has recently been shown to be phosphorylated by AMPK, providing a potential mechanism for localized PKA activity regulation by AMPK at mitochondria 27 .…”

Section: Ampk and Mitochondriamentioning

confidence: 99%

AMPK: guardian of metabolism and mitochondrial homeostasis

Herzig

Shaw

2017

Nat Rev Mol Cell Biol

2,310

1,702

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Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to reprogramme cellular metabolism from anabolism to catabolism. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.

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“…Noticeably, the caging efficiency in these systems is largely dependent on the interaction between target protein and the LOV domain [37,39]. Therefore, this strategy seems mostly applicable to small peptides, such as kinase inhibitory peptides [40,41] or protein trafficking peptides [42–46]. …”

Section: Regulation Of Protein Accessibility (Steric Caging)mentioning

confidence: 99%

Engineering genetically-encoded tools for optogenetic control of protein activity

Liu

Tucker

2017

Current Opinion in Chemical Biology

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Optogenetic tools offer fast and reversible control of protein activity with subcellular spatial precision. In the past few years, remarkable progress has been made in engineering photoactivatable systems regulating the activity of cellular proteins. In this review, we discuss general strategies in designing and optimizing such optogenetic tools and highlight recent advances in the field, with specific focus on applications regulating protein catalytic activity.

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

Cited by 172 publications

References 75 publications

Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

Adipocyte extracellular vesicles carry enzymes and fatty acids that stimulate mitochondrial metabolism and remodeling in tumor cells

AMPK: guardian of metabolism and mitochondrial homeostasis

Engineering genetically-encoded tools for optogenetic control of protein activity

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