The energy powerhouses of cells, called mitochondria, are much more dynamic than basic illustrations of cell organelles suggest. Mitochondria constantly split and fuse depending on the needs of the cell; they split when they need to move around the cell and fuse when they need to make energy that the cell can use.
New research from a team led by Jodi Nunnari, professor in the molecular and cell biology department of UC Davis, has just shown that proteins which help mitochondria fuse together (called MFN1 and MFN2) are the same proteins that protect against cell death. The two proteins must work together to regulate the frequency of fusion of mitochondria.
As scientists collect more data on how mitochondrial fusion and cell death is related, they hope to discover how diseases like Alzheimer’s develop and how those diseases can be stopped.
Nunnari’s team also found that a protein called Bax, which normally promotes cell death, takes another form that promotes mitochondrial fusion. Bax communicates with MFN2 to keep mitochondria fusion and cell death at a healthy level.
Both MFN1 and MFN2 are found in all cells, but at different ratios depending on the cell. In nerve cells, the most prevalent type is MFN2, which is the likely reason that human disease is most associated with mutations in MFN2 and rarely in MFN1. Since MFN2 is the protein that communicates with Bax, disease in the brain and nerves is likely related to protein miscommunication.
“It is very possible that some, if not all, degenerative neuropathies are due to a problem in communication between Bax and MFN2,” Nunnari said.
MFN1 and MFN2 are part of a class of proteins called dynamins that self-assemble in order to do various jobs maintaining cell machinery. Yeast, which is used very often in biological studies due to its simplicity, only has one type of fusion protein. Human and other cells have both types.
Using a mouse with the specific genes for the proteins “knocked-out” of its genome, the team was able to study how efficient different combinations of the proteins were for fusion. Because two proteins are required for fusion, the scientists tried combinations. They found that if the two proteins were different, mitochondrial fusion was more efficient than if the two proteins were the same.
The experiment is complicated because scientists don’t yet know how the MFN2 protein communicates with the Bax protein to accomplish fusion.
Suzanne Hoppins, a postdoctoral fellow in Nunnari’s lab, called the research “building blocks” as further study is needed before applications can be found.
“Our ultimate goal is to intelligently guide therapeutics,” Hoppins said.
According to Michael Sack, a doctor at the National Institutes of Health (NIH), “The understanding on how mitochondria are regulated and maintained is becoming increasingly apparent as the disruption in mitochondrial biology gives rise to a lot of degenerative diseases such as Alzheimer’s and Parkinson’s disease.”
Sack is the organizer of the 2011 National Heart, Lung and Blood Institute Mitochondrial Biology Symposium at which Jodi Nunnari will present her findings.
AMY STEWART can be reached at firstname.lastname@example.org.