Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2008 Jun 15;22(12):1577-90.
doi: 10.1101/gad.1658508.

Mitochondrial dynamics and apoptosis

Der-Fen Suen  1 , Kristi L Norris, Richard J Youle
Affiliations
Review

Mitochondrial dynamics and apoptosis

Der-Fen Suen et al. Genes Dev. .

Abstract

In healthy cells, mitochondria continually divide and fuse to form a dynamic interconnecting network. The molecular machinery that mediates this organelle fission and fusion is necessary to maintain mitochondrial integrity, perhaps by facilitating DNA or protein quality control. This network disintegrates during apoptosis at the time of cytochrome c release and prior to caspase activation, yielding more numerous and smaller mitochondria. Recent work shows that proteins involved in mitochondrial fission and fusion also actively participate in apoptosis induction. This review will cover the recent advances and presents competing models on how the mitochondrial fission and fusion machinery may intersect apoptosis pathways.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Mitochondrial fission machinery. Schematic of the localization of three proteins (Drp1, Fis1, and MARCH5) involved in mitochondrial fission in mammalian cells.
Figure 2.
Figure 2.
Outer mitochondrial morphology effects of Endophilin B1 knockdown. Confocal image of Endophilin B1/Bif1/SH3GLB1 knockdown by RNA interference in HeLa cells shows webs of OMM tubules (green) linking fragmented matrix compartments (red). Immunofluorescence of OMM is in green (α-Tom20) and the mitochondrial matrix is shown in red (α-TRAP1) (image by Chunxin Wang).
Figure 3.
Figure 3.
Mitochondrial fusion machinery. Schematic of the submitochondrial localization of mammalian proteins involved in mitochondrial fusion in healthy cells, including the mitofusins, OPA1, mitoPLD, and Bak (see key). Insert shows the localization of proteases proposed to function in OPA1 cleavage. Presenilin-associated rhomboid-like (PARL) is one member of the rhomboid family.
Figure 4.
Figure 4.
Cytochrome c release during apoptosis. Confocal image of multiple HeLa cells treated with actinomycin D and z-VAD-FMK (caspase inhibitor). Green represents cytochrome c immunofluorescence. (1) Healthy cells with long mitochondria and cytochrome c present in mitochondria. (2) During early stages of apoptosis, mitochondria fragment while some cytochrome c is retained in mitochondria. (3) Progressively later stages of apoptosis also have fragmented mitochondria, but cytochrome c is beginning to become visible in the cytosol. (4) Following complete release, cytochrome c is no longer within the mitochondria (image by Mariusz Karbowski). The time course for cytochrome c has been shown to be relatively fast and complete, indicating that mitochondrial fragmentation occurs immediately prior to or during the cytochrome c release process.
Figure 5.
Figure 5.
Competing models of mitochondrial morphogenesis machinery and apoptosis progression. (A) Mitochondrial foci model. From left to right, Bax (orange) translocates to mitochondria and coalesces into foci with Drp1, mitofusins, and Bak (see key), leading to mitochondrial division and release of cytochrome c (small red circles) from mitochondrial stores. (B) Cristae model of apoptosis. Drp1 (yellow) forms constriction sites on the OMM (left), then small amounts of cytochrome c from the intermembrane space are released through Bax/Bak pores (middle). (Right) Finally, cristae undergo remodeling, opening the junctions to release the larger amount of cytochrome c stored within the matrix.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abdelwahid E., Yokokura T., Krieser R.J., Balasundaram S., Fowle W.H., White K. Mitochondrial disruption in Drosophila apoptosis. Dev. Cell. 2007;12:793–806. - PubMed
    1. Adams J.M., Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26:1324–1337. - PMC - PubMed
    1. Alirol E., James D., Huber D., Marchetto A., Vergani L., Martinou J.C., Scorrano L. The mitochondrial fission protein hFis1 requires the endoplasmic reticulum gateway to induce apoptosis. Mol. Biol. Cell. 2006;17:4593–4605. - PMC - PubMed
    1. Arnoult D., Bartle L.M., Skaletskaya A., Poncet D., Zamzami N., Park P.U., Sharpe J., Youle R.J., Goldmacher V.S. Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria. Proc. Natl. Acad. Sci. 2004;101:7988–7993. - PMC - PubMed
    1. Arnoult D., Grodet A., Lee Y.J., Estaquier J., Blackstone C. Release of OPA1 during apoptosis participates in the rapid and complete release of cytochrome c and subsequent mitochondrial fragmentation. J. Biol. Chem. 2005a;280:35742–35750. - PubMed

MeSH terms

LinkOut - more resources