ºÙºÙÊÓƵ

A fundamental cellular event related to programmed cell death has been decoded by cell biologists at ºÙºÙÊÓƵ and Johns Hopkins University. The work could provide insights on two devastating inherited diseases.

In healthy cells, mitochondria (tiny energy substations that churn out each cell's power supply) continually fuse together and split in two. When mitochondrial fusion goes awry, cells are targeted for programmed cell death, or apoptosis.

Apoptosis is a normal process in healthy individuals, but if mitochondrial fusion doesn't work, the wrong cells die, causing disease. This is what happens in two neurodegenerative diseases: dominant optic atrophy, the most common inherited cause of blindness, and Charcot-Marie-Tooth disease, which reduces sensation in the feet, lower legs and hands. Both diseases kill nerve cells.

Until recently, scientists knew these diseases were triggered by a problem with mitochondrial fusion, but didn't understand fusion itself, says Jodi Nunnari, a ºÙºÙÊÓƵ professor of molecular and cellular biology.

Mitochondrial fusion was tricky to understand because mitochondria are structurally complex, Nunnari said. A mitochondrion looks a bit like an orange -- an outer membrane, analogous to the orange peel, contains it, while a different type of membrane on the inside facilitates the mitochondria's functions. Scientists wondered how two mitochondria could join without mixing up the distinct membranes.

Nunnari's team devised ways to get stop-action views of fusion and follow the process in isolated mitochondria. They saw two distinct stages. First, outer membranes joined, creating an intermediate structure with one outer membrane holding two sets of inner membranes. Then, the inner membranes fused. The researchers also were able to investigate some of the biochemical requirements for the process.

The work is published in the Sept. 17 issue of Science.