Researchers in Shanghai and the U.S. have unveiled a new cellular structure — the mitochondrial calcium uniporter (MCU), which supports cellular energy production — using two lab techniques, nuclear magnetic resonance and electron microscopy (EM). The study, “Architecture of the Mitochondrial Calcium Uniporter,“ appeared in the journal Nature.
Mitochondria are the cell’s power supply, generating energy in the form of adenosine triphosphate (ATP). Mitochondrial disorders affect an estimated 1 in every 2,000 people, and currently have no cure. Understanding the MCU could help facilitate new treatments for these chronic or inherited diseases.
Researchers in Professor James J. Chou’s lab at Shanghai Institutes for Biological Sciences, CAS, together with colleagues at Massachusetts General Hospital in Boston, examined the MCU in a model system known as Caenorhabditis elegans, a type of worm used widely in biological research due to the genetic similarity of many of its structures to humans.
They found, based on its putative structure, that the MCU is crucial for allowing the passage of ions, specifically calcium, into the mitochondria. It may have additional components as well, including a selectivity filter made up of two rings that allow the specific entry of calcium. Calcium entry into mitochondria is known to activate important pathways crucial for energy production, a process that can be impaired in people with mitochondrial diseases.
MCU is one of the biggest structures yet characterized by nuclear magnetic resonance (NMR). Understanding its structure could aid further studies of its functions.
“To our knowledge, this is one of the largest membrane protein structures characterized by NMR, and provides a structural blueprint for understanding the function of this channel,” the scientists reported.
This study was supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences, and by the U.S. National Institutes of Health and the Howard Hughes Medical Institute at Massachusetts General.
Mitochondrial diseases can occur either at birth or develop later, and are usually linked to development and cognition deficits. This type of disease may cause poor growth, lack of coordination, weakness, pain, and seizures.
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