I have been following articles by Dr. Muckenthaler ever since Two to Tango. She does publish on many topics, but it appears to me that she has a strong focus on unraveling the true mechanics of iron homeostasis. Therefore the HFE mutations are frequently featured in her papers. For example her latest paper is How mutant HFE causes hereditary hemochromatosis. In it she states: "...the underlying mechanisms differ: although the H63D variant failed to inhibit Alk3 ubiquitination, the HFE C282Y mutant protected ALK3 from ubiquitination, similar to wild-type HFE. The authors speculate that the HFE C282Y mutant protein that does not reach the cell membrane sequesters Alk3 inside cells, thereby preventing Alk3 from trafficking to the cell surface."
So our HFE mutations prevent increased Alk3 protein levels on the cell surface of hepatocytes (liver cells). Alk3 is critical to hepcidin expression. Without hepcidin, the body continuously recycles and absorbs iron leading to iron overload.
This is a significant finding because hepcidin is a huge and complex molecule which is very difficult to whereas Alk3 may be easier to manipulate pharmacologically.
For others that may be interested in keeping up with Dr. Muckenthaler, here is a handy link to her most recent publications.
So our HFE mutations prevent increased Alk3 protein levels on the cell surface of hepatocytes (liver cells). Alk3 is critical to hepcidin expression. Without hepcidin, the body continuously recycles and absorbs iron leading to iron overload.
This is a significant finding because hepcidin is a huge and complex molecule which is very difficult to whereas Alk3 may be easier to manipulate pharmacologically.
For others that may be interested in keeping up with Dr. Muckenthaler, here is a handy link to her most recent publications.