Fission and Fusion Among the Mitochondria

Two recently published studies describe advances in understanding how mitochondria, double-membrane bound intracellular organelles, divide and reform during the process of cell division.

Investigators at Johns Hopkins University (Baltimore, MD, USA), the California Institute of Technology (Palo Alto, USA), and the University of California, Davis (USA) used advanced optical and electronic microscope techniques to study mitochondria that had been isolated from their host cells.

They found that mitochondrial fission and subsequent fusion required mitofusin, an integral mitochondrial membrane protein. A seven amino acid repeat unit formed a coiled structure that spanned the membrane and allowed binding on either side. Mitochondrial outer and inner membrane fusion events were separable and mechanistically distinct, but both required energy supplied by guanosine 5'-triphosphate hydrolysis. These findings were reported in the August 6 and September 17, 2004, issues of Science.

"We observed two distinct stages, with the first involving outer membrane fusion yielding an intermediate structure of two conjoined mitochondria, followed by the subsequent fusion of the inner membranes giving rise to a single mitochondrion,” explained contributing author Dr. J. Michael McCaffery, director of the integrated imaging center at Johns Hopkins University. "Understanding the discrete molecular events that underlie dynamic mitochondrial behavior has the potential to reveal keen insights into the basic and essential cell-mitochondria relationship, leading to increased understanding of the aging process; and potential treatments and perhaps cures of those age-related scourges of Parkinson's and Alzheimer's.”