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Correlated three-dimensional light and electron microscopy reveals transformation of mitochondria during apoptosis.
- Source :
-
Nature cell biology [Nat Cell Biol] 2007 Sep; Vol. 9 (9), pp. 1057-65. Date of Electronic Publication: 2007 Aug 26. - Publication Year :
- 2007
-
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.
- Subjects :
- Antineoplastic Agents, Phytogenic pharmacology
Cytochromes c metabolism
Etoposide pharmacology
Fluorescent Dyes metabolism
HeLa Cells
Humans
Imaging, Three-Dimensional
Microscopy, Electron
Microscopy, Fluorescence methods
Mitochondria drug effects
Apoptosis physiology
Mitochondria ultrastructure
Subjects
Details
- Language :
- English
- ISSN :
- 1465-7392
- Volume :
- 9
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Nature cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 17721514
- Full Text :
- https://doi.org/10.1038/ncb1630