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ABCB6 is key to production of heme in hemoglobin

Investigators at St. Jude Children's Research Hospital have discovered that a protein called ABCB6 plays a central role in production of a molecule that is key to the ability of red blood cells to carry oxygen, of liver cells to break down toxins, and of cells to extract energy from nutrients.

The St. Jude investigators showed that ABCB6 is lodged within the outer membrane of the cell's energy powerhouse called the mitochondria; and that it ferries into mitochondria a type of molecule called a porphryin, a molecule essential for life. A report on these results appears in the advanced online publication of Nature.

Inside the mitochondrion, porphyrins are converted to heme. Heme is the oxygen-carrying part of the red blood cell molecule called hemoglobin, as well as a critical part of certain liver enzymes that break down toxins, and so-called "respiratory chain" enzymes in mitochondria that use oxygen to produce energy-rich molecules.

The discovery of the location and function of ABCB6 solved the long-standing riddle of how porphyrins get into mitchondria so they can be used to make heme, said John Schuetz, PhD, a member of St. Jude Pharmaceutical Sciences. "Porphyrins are negatively charged and so is the inside of mitochondria," Schuetz said. "So it wasn't clear how a negatively charged molecule could get into a negatively charged environment when it should have been repulsed--like two negative poles of a magnet pushing each other apart. Our work showed that ABCB6 overcomes that problem by simply grabbing porphyrin molecules and pulling them in.

"We showed that there is a dynamic relationship between ABCB6 and the levels of heme and porphyrin that helps to regulate the production of heme," Schuetz said. The team found that the increase in ABCB6 in mitochondrial membranes caused the cells to make more porphyrin, the building block of heme. "Any disruption of this relationship can cause serious problems in the cell by altering leve
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Source:St. Jude Children's Research Hospital


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