 |
 |
Mitochondria Mysteries Solved UCD researcher isolates process of mitochondrial fusion By PETER HAMILTON - Aggie Science Writer Wednesday November 03, 2004 The recent discoveries by a pair of UC Davis researchers will be added to the next edition of your basic biology textbook, providing insight into the complicated mechanisms behind a conceptually simple cellular process. Fifty years after the discovery of the intricate structure of DNA, the way mitochondria - components found in nearly all cells - divide and recombine was still unknown. That was until UCD researchers Shelly Meeusen and Jodi Nunnari published a paper in the journal Science this September revealing the intermediate steps of this pathway that had baffled biologists for decades. Mitochondria - tiny organelles within most eukaryotic cells where cellular energy is produced - constantly split and recombine within a cell. When this process malfunctions, the entire cell can die. Recent research suggests this might lead to a number of diseases, ranging from Alzheimer's to Parkinson's. Using yeast as her model, Meeusen was able to recreate the natural mitochondrial fusion process in vitro - in a test tube. This procedure had been attempted unsuccessfully for the past 20 years, and Meeusen was able to do it on one of her first attempts, according to Nunnari. With the entire process now removed from the cell and isolated in a test tube, Meeusen and Nunnari were able to manipulate the mitochondria to determine what is necessary for fusion to occur and what steps are involved in the process. "The [experiment] was basically where you have mitochondria with different colors and you mix them together," Meeusen said. "It's very simple how they co-localize, and you can learn so much from an assay like that." By marking separate mitochondria with different colors and then combining them, they were able to follow the pathways and processes that led up to, and completed fusion. "Because it's so visual," added Nunnari, "you not only get the end product, which is fusion, but you can actually analyze the structures of the intermediates because you can see them under the microscope." In two separate tubes containing many identical mitochondria, Meeusen and Nunnari inserted different DNA into each to make them literally glow different colors when viewed under special microscopes - some were made to be green, others red. When these green and red cells were added together in the same test tube they became yellow, the combination of both colors confirming their fusion. Nothing needed to be added to the test tubes for fusion to occur; the mitochondria produce everything they need to drive the reaction, from proteins to an energy source. "All the components are coded by genes in the mitochondria," Nunnari said. "The pathway of fusion has clearly evolved separately from other fusion reactions in the cell." For example, during regular cellular division, a cell requires many components contained within the cell. Without the skeletal microtubules and various "motors" necessary for division, cells would not be able to separate. But mitochondrial fusion and fission are distinctly different since it requires none of these other tools - partly why its mechanisms were so challenging to elucidate. Mitochondrial fusion requires four main components: Two were known - specific proteins and an energy source - but two were unique to Meeusen and Nunnari's experiment: proximity of the mitochondria and the membrane potential between them. In order for mitochondria to fuse, they must be very close together so that they can literally tether to each other via a complex of proteins. Only once attached can they begin to combine. "I think it was really critical to give the mitochondria a chance to dock, to interact, to get those complexes formed," Nunnari said. To achieve this, they centrifuged the cells to pack the mitochondria more densely. This might have helped to simulate conditions in the cell that are not possible in vitro, Nunnari said. Future work for Meeusen and Nunnari will focus on the characterization of the machinery of the inner membrane of the mitochondria and more mechanistic studies of the different stages of fusion. PETER HAMILTON can be reached at [log in to unmask] SOURCE: The California Aggie Online http://www.californiaaggie.com/article/?id=6126 * * * Murray Charters <[log in to unmask]> Please place this address in your address book Please purge all others Web site: Parkinsons Resources on the WWWeb http://www.geocities.com/murraycharters ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn