The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis

Ruth M. Kluck; Ella Bossy‐Wetzel; Douglas R. Green; Donald D. Newmeyer

doi:10.1126/science.275.5303.1132

Abstract

In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology. Bcl-2 acted in situ on mitochondria to prevent the release of cytochrome c and thus caspase activation. During apoptosis in intact cells, cytochrome c translocation was similarly blocked by Bcl-2 but not by a caspase inhibitor, zVAD-fmk. In vitro, exogenous cytochrome c bypassed the inhibitory effect of Bcl-2. Cytochrome c release was unaccompanied by changes in mitochondrial membrane potential. Thus, Bcl-2 acts to inhibit cytochrome c translocation, thereby blocking caspase activation and the apoptotic process.

Keywords

Cytochrome cApoptosomeApoptosisMitochondrionMitochondrial apoptosis-induced channelCell biologyCaspaseCytochromeIntrinsic apoptosisBiologyCaspase-9ChemistryMolecular biologyProgrammed cell deathBiochemistryEnzyme

Affiliated Institutions

La Jolla Institute for Immunology US

Related Publications

Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization

Ella Bossy‐Wetzel

Mitochondrial cytochrome c, which functions as an electron carrier in the respiratory chain, translocates to the cytosol in cells undergoing apoptosis, where it participates in ...

1998 The EMBO Journal 1226 citations

Bax directly induces release of cytochrome <i>c</i> from isolated mitochondria

Juliane M. Jürgensmeier , Zhihua Xie , Quinn L. Deveraux +3 more

Bax is a pro-apoptotic member of the Bcl-2 protein family that resides in the outer mitochondrial membrane. It is controversial whether Bax promotes cell death directly through ...

1998 Proceedings of the National Academy o... 1512 citations

Apoptosis Induction by Caspase-8 Is Amplified through the Mitochondrial Release of Cytochrome c

Tomomi Kuwana , J. Joshua Smith , Marta Muzio +3 more

Apoptosis often involves the release of cytochrome c from mitochondria, leading to caspase activation. However, in apoptosis mediated by CD95 (Fas/APO-1), caspase-8 (FLICE/MACH/...

1998 Journal of Biological Chemistry 376 citations

Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked

Jie Yang , Xuesong Liu , Kapil N. Bhalla +6 more

Bcl-2 is an integral membrane protein located mainly on the outer membrane of mitochondria. Overexpression of Bcl-2 prevents cells from undergoing apoptosis in response to a var...

1997 Science 4912 citations

Tumor necrosis factor α induces a caspase-independent death pathway in human neutrophils

Nikolai A. Maianski , Dirk Roos , Taco W. Kuijpers

Tumor necrosis factor α (TNF-α) is a cytokine with multiple roles in the immune system, including the induction and potentiation of cellular functions in neutrophils (PMNs). TNF...

2003 Blood 123 citations

Publication Info

Year: 1997
Type: article
Volume: 275
Issue: 5303
Pages: 1132-1136
Citations: 4716
Access: Closed

External Links

View on DOI.org

Social Impact

Altmetric

The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

4716

OpenAlex

Cite This

APA Style

                            
                                
                                    Ruth M. Kluck, 
                                
                                    Ella Bossy‐Wetzel, 
                                
                                    Douglas R. Green
                                
                                et al.
                            
                            (1997). 
                            The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis. 
                            Science
                            , 275
                            (5303)
                            , 1132-1136.
                            https://doi.org/10.1126/science.275.5303.1132
                        

Identifiers

DOI: 10.1126/science.275.5303.1132