Balancing the brain

The MTCH2 gene (pronounced Mitch 2) has been the focus of our lab for over a decade. MTCH2 was discovered in our lab in 2005: It is a protein that sits on the outer membrane of the cellular organelles called mitochondria – often known as the cells’ “power plants.” We have found, among other things, that MTCH2 is involved in cell suicide, in metabolism and metabolic diseases, and more recently in neurodegenerative diseases.

Our lab and the Segal lab wanted to determine what would be the outcome of knocking out MTCH2 in the mice’s brains, and our collaboration enabled us to analyze the effect on both the molecular level and the level of whole neurons, as well as that of the nervous system as a whole. Our findings, which recently appeared in Scientific Reports, revealed that the ability of the mitochondria to move around in the cell was impaired, as was the balance of calcium inside the neuron. Calcium is especially crucial to signaling between nerve cells, so even slight variations in levels of this element within the neurons could interrupt their normal activity.

For Segal, the connection between balancing calcium and memory was unsurprising. He and his lab have been engaged, in recent years, in advancing a new approach to Alzheimer’s research that focuses in calcium, rather than the accepted one that blames the disease on amyloid plaques in the brain. “Billions of dollars are invested in finding a way to prevent these plaques, but it is still not clear whether the plaques are a cause or effect, or simply a parallel symptom of aging,” he says. “This study gives us some new leads on the way that the handling of calcium within the cell may be disrupted with age as the mitochondria function drops and how this dysfunction ties into a decline in mental function.”

The study was led by research student Antonella Ruggiero in our lab, and conducted together with Dr. Yehudit Zaltsman of our lab; research student Etay Aloni, Dr. Eduard Korkotian and Efrat Oni-Biton of Segal’s lab; Drs. Yael Kuperman, Michael Tsoory and Ori Brenner of the Institute’s Veterinary Services and Dr. Smadar Levin-Zaidman of the Chemical Research Support Department.

A collaboration between a lab that studies the molecular processes of individual metabolic proteins and another that does brain research is uncommon, but the partnership has been fruitful for both. We had to find common ground and fortunately we did. We also love to work together because it allows us to probe everything from the finest details to the big picture – from molecules to an entire system.

Our labs are continuing to collaborate in an effort to answer questions this research has raised, for example: How does MTCH2 cause changes in the cell’s calcium levels and how is the movement of the mitochondria involved in memory and learning?