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PMID: 11309413 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Cytochrome c maintains mitochondrial transmembrane potential and ATP generation after outer mitochondrial membrane permeabilization during the apoptotic process.

The Journal of cell biology ·Vol. 153 ·No. 2 ·2001-04-16 ·Pages 319-28

Waterhouse NJ, Goldstein JC, von Ahsen O, Schuler M, Newmeyer DD, Green DR

Abstract

During apoptosis, cytochrome c is released into the cytosol as the outer membrane of mitochondria becomes permeable, and this acts to trigger caspase activation. The consequences of this release for mitochondrial metabolism are unclear. Using single-cell analysis, we found that when caspase activity is inhibited, mitochondrial outer membrane permeabilization causes a rapid depolarization of mitochondrial transmembrane potential, which recovers to original levels over the next 30-60 min and is then maintained. After outer membrane permeabilization, mitochondria can use cytoplasmic cytochrome c to maintain mitochondrial transmembrane potential and ATP production. Furthermore, both cytochrome c release and apoptosis proceed normally in cells in which mitochondria have been uncoupled. These studies demonstrate that cytochrome c release does not affect the integrity of the mitochondrial inner membrane and that, in the absence of caspase activation, mitochondrial functions can be maintained after the release of cytochrome c.

MeSH Terms
Amino Acid Chloromethyl Ketones/pharmacology Animals Apoptosis/physiology Caspase Inhibitors Caspases/metabolism Cells, Cultured Cytochrome c Group/metabolism Dactinomycin/pharmacology Fibroblasts/physiology Flow Cytometry Fluorescent Dyes/metabolism Green Fluorescent Proteins Humans Intracellular Membranes/metabolism Luminescent Proteins/metabolism Membrane Potentials/physiology Mice Microscopy, Confocal Mitochondria/drug effects,physiology Protein Synthesis Inhibitors/pharmacology Proto-Oncogene Proteins c-bcl-2/metabolism Recombinant Fusion Proteins/metabolism Time Factors Uncoupling Agents/pharmacology
Chemicals
Amino Acid Chloromethyl Ketones Caspase Inhibitors Cytochrome c Group Fluorescent Dyes Luminescent Proteins Protein Synthesis Inhibitors Proto-Oncogene Proteins c-bcl-2 Recombinant Fusion Proteins Uncoupling Agents benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone Green Fluorescent Proteins Dactinomycin Caspases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Waterhouse N J
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.
Goldstein J C
von Ahsen O
Schuler M
Newmeyer D D
Green D R
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.153.2.319
Published
2001-04-16
Pages
319-28
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2169468
Subset
IM
Grants
NIAID NIH HHS · AI40646 · United States
NCI NIH HHS · CA69381 · United States
External Links
PubMed source DOI: 10.1083/jcb.153.2.319 PMC Full Text View journal details
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