Researchers at Massachusetts General Hospital (MGH) have developed a new way to alleviate problems caused by dysfunctional mitochondria, which are the “powerhouses” that produce energy in cells. Their discovery, reported in the journal Nature Biotechnology on January 13, could lead to a new treatment for rare diseases caused by “broken” mitochondria, but could also be used to develop novel therapies for more common age-associated disorders.
All cells have mitochondria. “Mitochondria take electrons from the food we eat and transfer them to oxygen,” explains Vamsi Mootha, MD, investigator in the Department of Molecular Biology at MGH, and senior author of the Nature Biotechnology paper. Mootha compares this process to a river flowing down a mountain, with water wheels that harness the flow to produce energy.
However, mitochondrial disorders act like a dam by blocking this smooth flow and causing a pileup of electrons, known as a redox imbalance, and stalling vital chemical reactions inside the cell. “We think toxicity is coming from the fact that the ‘waterwheel’ is no longer spinning,” says Mootha. The excess electrons eventually spill into blood circulation in the form of lactate, a molecule that serves as a marker for the disease occurring inside the cells.
Malfunctioning mitochondria cause more than 300 rare genetic disorders, such as Leigh syndrome (a crippling neurological disease that can present early in infancy) and MELAS (which causes muscle weakness, diabetes, and strokes, with onset usually before age 40). However, a gradual fall-off in mitochondrial function also occurs in Parkinson’s disease and other more common disorders. “Even the aging process itself, absent disease, is associated with a decline in mitochondrial activity,” says Mootha.
