Letter abstract


Nature Cell Biology 9, 1057 - 1065 (2007)
Published online: 26 August 2007 | doi:10.1038/ncb1630

Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis

Mei G. Sun1, James Williams1, Cristina Munoz-Pinedo2, Guy A. Perkins3, Joshua M. Brown3, Mark H. Ellisman3, Douglas R. Green2 & Terrence G. Frey1

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In addition to their role in cellular bioenergetics, mitochondria also initiate common forms of programmed cell death (apoptosis) through the release of proteins such as cytochrome c from the intermembrane and intracristal spaces1, 2. The release of these proteins is studied in populations of cells by western blotting mitochondrial and cytoplasmic fractions of cellular extracts, and in single cells by fluorescence microscopy using fluorescent indicators and fusion proteins3, 4. However, studying the changes in ultrastructure associated with release of proteins requires the higher resolution provided by transmission electron microscopy5, 6, 7. Here, we have used fluorescence microscopy to characterize the state of apoptosis in HeLa cells treated with etoposide followed by electron microscopy and three-dimensional electron microscope tomography of the identical cells to study the sequence of structural changes. We have identified a remodelling of the inner mitochondrial membrane into many separate vesicular matrix compartments that accompanies release of proteins; however, this remodelling is not required for efficient release of cytochrome c. Swelling occurs only late in apoptosis after release of cytochrome c and loss of the mitochondrial membrane potential.

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  1. Department of Biology, San Diego State University, San Diego, CA 92182-4614, USA.
  2. Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105–2794, USA.
  3. Center for Research in Biological Systems, National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA 92093-0608, USA.

Correspondence to: Terrence G. Frey1 e-mail: tfrey@sunstroke.sdsu.edu




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