Taking heart failure to the MAT1
A gene called ménage-à-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.
In fact, two forms of PGC-1 exist — alpha and beta — both of which have been reported by other groups to be vital to the heart. Both forms of PGC-1 were shown by Schneider's team to depend highly on MAT1 and to turn on the ordinarily responsive genes for energy production in heart tissue.
"One of the problems in failing hearts is that energy production is deficient," said Schneider. "Drugs that act on the PPARs (peroxisome proliferator activated receptors) and other nuclear receptors to promote better metabolism are a very active area of study. Finding an essential partner of PGC-1 alpha and beta that enables them to switch genes on via these receptors should be helpful in that kind of work."
Ross Tomlin | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...