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

Mei G. Sun, James Williams, Cristina Munoz-Pinedo, Guy A. Perkins, Joshua M. Brown, Mark H. Ellisman, Douglas R. Green, Terrence G. Frey

Research output: Contribution to journalArticle

167 Citations (Scopus)

Abstract

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 spaces. 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 proteins. However, studying the changes in ultrastructure associated with release of proteins requires the higher resolution provided by transmission electron microscopy. 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.

Original languageEnglish (US)
Pages (from-to)1057-1065
Number of pages9
JournalNature Cell Biology
Volume9
Issue number9
DOIs
StatePublished - Sep 2007
Externally publishedYes

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Electron Microscopy
Mitochondria
Apoptosis
Light
Cytochromes c
Proteins
Fluorescence Microscopy
Electron Microscope Tomography
Mitochondrial Membrane Potential
Mitochondrial Membranes
Etoposide
Transmission Electron Microscopy
HeLa Cells
Energy Metabolism
Cell Death
Western Blotting
Population

ASJC Scopus subject areas

  • Cell Biology

Cite this

Sun, M. G., Williams, J., Munoz-Pinedo, C., Perkins, G. A., Brown, J. M., Ellisman, M. H., ... Frey, T. G. (2007). Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis. Nature Cell Biology, 9(9), 1057-1065. https://doi.org/10.1038/ncb1630

Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis. / Sun, Mei G.; Williams, James; Munoz-Pinedo, Cristina; Perkins, Guy A.; Brown, Joshua M.; Ellisman, Mark H.; Green, Douglas R.; Frey, Terrence G.

In: Nature Cell Biology, Vol. 9, No. 9, 09.2007, p. 1057-1065.

Research output: Contribution to journalArticle

Sun, MG, Williams, J, Munoz-Pinedo, C, Perkins, GA, Brown, JM, Ellisman, MH, Green, DR & Frey, TG 2007, 'Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis', Nature Cell Biology, vol. 9, no. 9, pp. 1057-1065. https://doi.org/10.1038/ncb1630
Sun, Mei G. ; Williams, James ; Munoz-Pinedo, Cristina ; Perkins, Guy A. ; Brown, Joshua M. ; Ellisman, Mark H. ; Green, Douglas R. ; Frey, Terrence G. / Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis. In: Nature Cell Biology. 2007 ; Vol. 9, No. 9. pp. 1057-1065.
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