A scientific collaboration between researchers in Scotland and China has uncovered a new kind of `energy sensor' in our cells, changing our understanding of how the body monitors glucose levels and switches on the supply of alternative `fuels'.
It is thought the research, published in the journal Nature, could have particular implications for diabetes, in which the level of glucose in the blood is abnormally high.
The research focused on the activity of a protein called AMPK. The AMPK enzyme is switched on when energy levels in the cell fall, and drives processes which stimulate energy production, while preventing energy-consuming processes.
AMPK is important because it enables the body to start burning other `fuels'. For example, during exercise, when the demand for energy is dramatically increased in muscle, AMPK switches on the uptake and metabolism of glucose and fats to provide the required energy.
It has been known for years that starving cells of glucose switches on AMPK, but everyone had assumed that this worked via the known ability of AMPK to sense changes in the cell's energy status. It is unclear whether activation of AMPK occurs solely via changes in AMP or ADP, the classical activators of AMPK.
Authors show an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation.
Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation.
Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation.
These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.
"We have now shown that cells can actually sense glucose by a completely different mechanism, in which AMPK is recruited to structures called lysosomes. It is by doing this that cells can switch on pathways for metabolism of alternative fuels, such as fats, when glucose becomes scarce but before cellular energy declines."
Senior author said more work would be needed to understand the full implications of this for human health. However, given the extremely prominent role of glucose in diabetes it is likely to be of significant value in understanding more about the disease.
AMPK is thought to be implicated in other conditions and diseases, including obesity and cancer.
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature23275.html?foxtrotcallback=true
Alternate energy switch in the cells identified!
- 3,255 views
- Added
Edited
Latest News
DNA attached to nanoparticl…
By newseditor
Posted 29 Mar
Neighboring synapses shape…
By newseditor
Posted 29 Mar
Complete vascularization of…
By newseditor
Posted 28 Mar
Immune cells identified as…
By newseditor
Posted 28 Mar
TB blood test which could d…
By newseditor
Posted 27 Mar
Other Top Stories
The biological clock influences immune response efficiency
Read more
Immune cell atlas of the human kidney
Read more
Reversing multiple sclerosis in mice by targeting specific T cell s…
Read more
Proteomics of T cell differentiation!
Read more
A protein could play a key role in inflammatory response in brain
Read more
Protocols
Spatial proteomics in neuro…
By newseditor
Posted 28 Mar
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Publications
DNA corona on nanoparticles…
By newseditor
Posted 29 Mar
Co-dependent excitatory and…
By newseditor
Posted 29 Mar
A microfluidic platform int…
By newseditor
Posted 28 Mar
Salmonella manipulates macr…
By newseditor
Posted 28 Mar
BHLHE40/41 regulate microgl…
By newseditor
Posted 28 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar