How MCUR1 Dictates Calcium Load
In the current study, Drs. Madesh and Foskett and their co-workers may have come closer to solving this puzzle. Dr. Madesh and his group sought to identify the genes involved in the flow of calcium into the mitochondria. They developed a way to use a technology called targeted RNA interference (RNAi) to screen 50 mitochondrial proteins, systematically testing whether eliminating the function of each of these genes individually altered the movement of calcium into the mitochondria. They found a mitochondrial inner membrane protein MCUR1 that regulates a calcium channel pore during active calcium uptake.
MCUR1 is part of a calcium channel pore called the uniporter, the existence of which has been known for some five decades. Recent studies identified two important pieces of the pore a subunit protein, MCU, and the gatekeeper protein, MICU1, to maintain calcium levels at a resting, set point. The researchers found that MCUR1 interacts with MCU to accelerate the movement of calcium into mitochondria when the cell's calcium level rapidly rises.
"MCUR1 is an essential third component of the uniporter complex," Dr. Madesh said. "In the absence of MCUR1, mitochondrial calcium uptake is markedly reduced, with adverse cellular consequences, including compromised cellular bioenergetics."
Without this accelerator, the mitochondria channel pore alone cannot take up calcium. When MCUR1 is physically attached to the pore, it is functional, and when it is not attached, it is much less active. "The regulator is always on
|Contact: Steven Benowitz|
Temple University Health System