Lauren Walters talks about her poster with James Sligh Jr., M.D., Ph.D., one of the speakers at the recent Vanderbilt Genetics Symposium. (photo by Neil Brake)
Genetics Symposium sheds light on cells’ internal ‘power plants’
Mitochondria — the “power plants” of cells — are central to life and science, speakers at last week's 8th annual Vanderbilt Genetics Symposium said.
“Energy is life, and mitochondria are about energy,” said Douglas Wallace, Ph.D., director of the Center for Molecular and Mitochondrial Medicine and Genetics at the University of California, Irvine, and one of three visiting speakers at the daylong event. He likened the cell to a house, where the information for the design-and-build resides in the nucleus, but the wiring diagrams — the energy circuits — reside in the mitochondria.
“These are not trivial structures in the cell,” Wallace said.
Mitochondria have their own genome, a circular form of DNA that resembles the bacterial genomes from which it is thought to derive. The mitochondrial genome includes only 37 genes (compared to the 20,000 or more genes present in the cell nucleus), but mutations and variations in the mitochondrial genome are being increasingly linked to disease.
In the 1970s, Wallace and colleagues defined the basic principles of mitochondrial genetics, demonstrating that traits encoded by human mitochondrial DNA can be inherited, that the mitochondrial genome is passed on by the mother, and that mitochondrial DNA has a high mutation rate.
Because only women can pass mitochondrial DNA to the next generation, men are “dead ends,” joked Jeffrey Canter, M.D., M.P.H., professor of Molecular Physiology & Biophysics and one of the Vanderbilt speakers at the event.
“A man has done all he can ever be expected to do when he has a daughter,” Canter said, showing a list of the “successful” Center for Human Genetics Research male faculty members and their daughters.
Canter detailed his team's studies showing associations between mitochondrial DNA variation and prostate cancer, breast cancer, age-related macular degeneration and trauma survival.
The idea that genetic variation — particularly in mitochondrial DNA — plays a role in trauma survival is a new one, with encouraging initial results, Canter said. Trauma/unintentional injury accounts for 35 percent of all deaths for people age 1 to 44.
“Trauma survival is an underappreciated phenotype, and it's appropriate that an underappreciated genome (the mitochondrial genome) may be linked to it,” Canter said.
In addition to providing most of the energy in the cell, mitochondria play a key role in programmed cell death (apoptosis), and they also generate “reactive oxygen species” — free radicals that can damage the cell, including the mitochondrial DNA.
Wallace argued that mutations in the mitochondrial DNA alter the efficiency of the mitochondria, lead to the over-production of reactive oxygen species, and switch on cell death mechanisms, accounting for many metabolic and degenerative diseases as well as aging-related changes and cancer.
Other visiting speakers included Robert Naviaux, M.D., Ph.D., co-director of the Mitochondrial and Metabolic Disease Center at the University of California, San Diego, and Jodi Nunnari, Ph.D., professor of Molecular and Cellular Biology at the University of California, Davis.