A recent study has explained why some body organs are more susceptible to cell death than others. This finding would eventually lead to advanced treatment or prevention of heart attack or stroke.
The UC Davis team and their collaborators at the National Institutes of Health and Johns Hopkins University report that Bax, a factor known to promote cell death, is also involved in regulating the behavior of mitochondria, the structures that provide energy inside living cells.
Mitochondria constantly split and fuse. The proteins that control the splitting of mitochondria also promotes a process called apoptosis, or programmed cell death.
Both human and mouse cells have two proteins, called MFN1 and MFN2, which control outer membrane fusion.
Using mitochondria from cells derived from genetically modified "knockout" mice, Suzanne Hoppins and Jodi Nunnari at UC Davis, studied how these two proteins work together and the role specific genes play in that process.
The research team discovered that these proteins combine with themselves or each other to form a tether between two mitochondria, leading to fusion.
Hoppins also found that a soluble form of Bax, a protein that triggers apoptosis, can also stimulate mitochondria to fuse. It acts only through the MFN2/MFN2 combination, she found.
The form of Bax that promotes mitochondrial fusion is different from the type that leads to cell death, Nunnari said. Bax leads to cell death when it inserts itself in the mitochondrial membrane. In its soluble, free-floating form, it causes mitochondria to fuse instead.
MFN1 and MFN2 are found in different amounts in different body organs. MFN2 is more abundant in the brain and heart tissues where cell death can have disastrous consequences.
The paper shows how MFN2 could act to protect the brain or heart from cell death, by using Bax in a different form, Nunnari said.
The research has been published Jan. 21 in the journal Molecular Cell.