Mitochondria have been found to also be the driver with regard to cell division, according to a group of biochemists who say this discovery could play a large role in finding cures for many human diseases. The scientists studied yeast cells and found that mitochondria, which generate 90 percent of the cell’s energy, can be the deciding factor behind how fast cells divide. The finding by Michael Polymenis and Mary Bryk and their research groups is published today in the open-access journal PLoS Genetics. The finding changes the traditional view of the mitochondrion from an “energy depot” at the service of its larger cellular host to a “command center” that directs cell division. The researchers used regular baker’s yeast (Saccharomyces cerevisiae) – commonly used in bread, wine and beer making – because many of the yeast cell’s processes are similar to those in human cells. From unicellular yeast to complex mammals, the process is the same. The job of a cell is to divide and grow. Metabolism takes in “food” and turns it into fuel and building blocks for DNA replication and gene expression. But when these processes falter, diseases can result. Too much cell division too quickly, for example, is typical of cancerous cells. Conversely, poor metabolism – stemming from mitochondrial deficiencies – is at the root of damage to various organs such as the brain, heart, skeletal muscles, and liver. All of the body processes that require a lot of energy are impacted by this, and at least 1 in every 4,000 people worldwide suffer from mitochondrial deficiencies that result in problems with normal development, motor control, vision, hearing, or liver and kidney function. Alternatively, there are times when speeding cell division might be useful as with wound healing and plant or crop production. If we can understand the basic pathway that regulates cell division, we can think of ways to tweak the different steps in that path with therapeutics to help people who have problems with these high-energy organs. The research showed that when a yeast cell’s mitochondria decided to “turn on the switch,” the cell’s nucleus, which carries most of the genetic material, received the message and cell division began. So now we need to connect that link. We need to understand how and when the mitochondria send the message. If we know how the message is sent, we might be able to control it.
Coordination between cellular metabolism and DNA replication determines when cells initiate division. It has been assumed that metabolism only plays a permissive role in cell division. While blocking metabolism arrests cell division, it is not known whether an up-regulation of metabolic reactions accelerates cell cycle transitions. Here, we show that increasing the amount of mitochondrial DNA accelerates overall cell proliferation and promotes nuclear DNA replication, in a nutrientdependent manner. The Sir2p NAD+-dependent de-acetylase antagonizes this mitochondrial role. We found that cells with increased mitochondrial DNA have reduced Sir2p levels bound at origins of DNA replication in the nucleus, accompanied with increased levels of K9, K14-acetylated histone H3 at those origins. Our results demonstrate an active role of mitochondrial processes in the control of cell division. They also suggest that cellular metabolism may impact on chromatin modifications to regulate the activity of origins of DNA replication.
An Increase in Mitochondrial DNA Promotes Nuclear DNA Replication in Yeast. 2008 PLoS Genet 4(4): e1000047