Mcl1 Promotes Endothelial Senescence And Atherosclerosis Via Glycolytic Reprogramming-Induced H4K12 Lactylation
Atherosclerosis, a condition where plaque builds up inside arteries, is a major health concern. A key factor in its development is the aging of the cells lining our blood vessels, known as endothelial cells. Recent research has shed light on a crucial player in this process: a protein called MCL1.
Scientists discovered that MCL1 is present in higher amounts in diseased arteries and in aging endothelial cells. This protein essentially “reprograms” how these cells produce energy, shifting them towards a process called glycolysis. Glycolysis is a way cells generate energy, but in this context, it leads to an accumulation of lactate, a byproduct.
This excess lactate isn’t just waste; it plays an active role in modifying the cell’s genetic material. It causes a specific change called H4K12 lactylation on histones, which are proteins that help package DNA. This modification acts like a switch, turning on certain genes, particularly one called P21, which is known to promote cell aging. The result is an acceleration of endothelial cell aging and, consequently, the worsening of atherosclerosis.
Understanding this intricate connection between MCL1, energy metabolism, and genetic modifications opens up exciting possibilities. Targeting this MCL1-related pathway could offer a promising new strategy for developing treatments to combat atherosclerosis.
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