In a collaborative study between U of T and several institutions around the globe, researchers have discovered that a molecule called EXD2 plays a significant role in the metabolic processes that occur in mitochondria. Prior to this study, EXD2’s function and location within a cell were unclear.
Mitochondria are mini organ-like structures in our cells that produce the daily energy we need to survive through a variety of metabolic processes. Often called the powerhouse of the cell, the proteins that are made by the mitochondria to provide this daily energy are crucial to human growth and longevity.
Previous studies reported that EXD2 plays a role in DNA damage and thus would likely be found in the nucleus, where DNA is also located.
However, the researchers from this study compared EXD2’s genome to others in a database and discovered a segment that resembled a mitochondrial target sequence — these sequences direct proteins to the mitochondria. They tagged EXD2 with a fluorescent marker and found that it primarily localized to the mitochondria rather than to the nucleus.
Using nuclear magnetic resonance, a technique that allows researchers to study the structure of molecules, the researchers discovered that depleting EXD2 levels causes aberrations in several metabolic processes, such as limiting the incorporation of glucose-derived carbon into several molecules involved in metabolism.
They also found that EXD2 affects mitochondrial translation, a process that cells use to make proteins. The researchers used a method called metabolic pulse labeling to determine that mitochondrial translation rates are lower in cells that lack EXD2.
The researchers also studied the effects of EXD2 in Drosophila melanogaster, otherwise known as the common fruit fly. Flies deficient in the Drosophila version of EXD2, called dEXD2, exhibited impaired metabolic processes such as cellular respiration, decreased body size, developmental delays, decreased germ stem cell numbers, and increased lifespan.
Without EXD2, the mitochondria cannot effectively synthesize the proteins needed to provide energy for the cell. This collaborative study has opened up a new window of opportunities in the field of cellular metabolism by providing a new perspective on aging, development, and metabolism.