A gene called mnage--trois 1, or MAT1, plays a crucial role in the function of a master switch for production of energy in the heart cell -- a finding that has important implications for understanding and maybe even treating heart failure, said researchers from Baylor College of Medicine and other institutions in a report published in today's issue of the journal Cell Metabolism.
When Dr. Michael Schneider, professor of medicine, molecular & cellular biology, and molecular physiology & biophysics at BCM, and his colleagues studied infant mice that lacked this gene in their heart muscle cells, "We found that the hearts grew normally. This was surprising, in view of some postulated functions of MAT1. But when the animals reached five weeks of age, they began to succumb to catastrophic heart failure, and all of them were dead by two months."
Using "gene chip" technology, the researchers looked for abnormal patterns of gene expression in hearts from which the MAT1 gene was deleted. They found that genes controlling energy production in cells were particularly affected and that the cells had correspondingly low levels of the proteins required for energy production. The mitochondria -- the cell's energy factories -- were defective.
Further research showed that a particular protein called peroxisome proliferator-activated receptor-1 coactivator, or PGC-1, which is a known master regulator of energy production by cells, did not function in cells that lacked MAT1. Even when the scientists artificially increased the amount of PGC-1 in the cells, its function was decreased if there was no MAT1.
Ultimately, the investigators proved that MAT1 binds to PGC-1 and forms a physical complex with it, providing a direct biochemical explanation for the ability of MAT1 to serve as an essential partner to PGC-1, facilitating its role in regulating cell metabolism.