University of California researchers have discovered an approach that may help treat patients with some chronic inflammatory diseases, as published in Cell Metabolism. They found that, by forcing cells to eliminate damaged mitochondria before they activate the immune molecule NLRP3 inflammasome, they may decrease excess inflammation, the main cause to numerous diseases including Alzheimer’s and cancer.

Immune cells utilize specialized molecules called NLRP3 inflammasome to help keep tabs on inflammation. NLRP3 is inactive in healthy cells, but when “switched on”, the cell’s mitochondria can become damaged by stress or exposure to bacterial toxins. Excess NLRP3 inflammasomes can contribute to a number of chronic inflammatory conditions including Alzheimer’s disease, gout, fatty liver disease, and osteoarthritis.

It has been shown that damaged mitochondria activate NLRP3 inflammasomes, and that the inflammasome is deactivated when mitochondria are removed by the cell’s internal mitophagy recycling process. This is what is supposed to take place in healthy individuals.

The research showed how macrophages (a specialized immune cell) regulate uptake of choline and the team discovered that an inhibitor of the enzyme Choline Kinase could initiate mitophagy (cell recycling).  With Choline Kinase inhibited, choline was no longer incorporated into mitochondrial membranes, leaving the mitochondria “damaged”, sparking the NLRP3 inflammasome pathway, causing chronic, excess, damaging inflammation.

Incorporating choline into the diet – the best source is Phosphatidylcholine – may be a huge step forward to protect mitochondial and cell membranes as well as aide mitophagy.

“Choline is a vitamin-like nutrient that is taken up via specific transporters and metabolized by choline kinase, which converts it to phosphocholine needed for de novo synthesis of phosphatidylcholine (PC), the main phospholipid of cellular membranes. We found that Toll-like receptor (TLR) activation enhances choline uptake by macrophages and microglia through induction of the choline transporter CTL1. Inhibition of CTL1 expression or choline phosphorylation attenuated NLRP3 inflammasome activation and IL-1β and IL-18 production in stimulated macrophages. Mechanistically, reduced choline uptake altered mitochondrial lipid profile, attenuated mitochondrial ATP synthesis, and activated the energy sensor AMP-activated protein kinase (AMPK). By potentiating mitochondrial recruitment of DRP1, AMPK stimulates mitophagy, which contributes to termination of NLRP3 inflammasome activation. Correspondingly, choline kinase inhibitors ameliorated acute and chronic models of IL-1β-dependent inflammation,” according to the researchers.