"In this study, we show that MCL1 has two forms and two important, but completely different functions," said Rhonda Perciavalle, Ph.D., a University of Tennessee Health Science Center graduate student in Opferman's laboratory and the study's first author. Along with working on the outer mitochondrial membrane to help protect cells from apoptosis, investigators demonstrated that MCL1 works internally to facilitate mitochondrial energy production in the mitochondrion's matrix.
Using a variety of laboratory techniques, researchers showed that inside the mitochondrion, MCL1 promotes the normal structure of the inner membrane, where much of the work of energy production is done. The loss of the inner mitochondrial form of MCL1 hampers the ability of cells to produce energy, thus impeding their ability to proliferate.
"The results help explain why the loss of this single pro-survival molecule, MCL1, has such a dramatic impact. We are now working with tumor models to determine if this newly identified form of MCL1 is essential for cancer cells," Opferman said. Perciavalle said the two forms might work together to protect cancer cells from apoptotic death and to provide them with the fuel and nutrients to sustain their unchecked growth and spread.
Work is also underway to learn precisely how MCL1 functions inside the mitochondria in both normal and cancer cells. Investigators are also interested in the relative importance of the two versions of MCL1 in different tissues under a variety of different conditions.
|Contact: Summer Freeman|
St. Jude Children's Research Hospital