Regulation of cellular oncosis by uncoupling protein 2

Edward M. Mills, Dong Xu, María M. Fergusson, Christian A. Combs, Yuhui Xu, Toren Finkel

Research output: Contribution to journalArticle

Abstract

Cell death can proceed through at least two distinct pathways. Apoptosis is an energy-dependent process characterized morphologically by cell shrinkage, whereas oncosis is a form of cell death induced by energy depletion and initially characterized by cell swelling. We demonstrate in HeLa cells but not in normal diploid fibroblasts that modest increases in the expression level of uncoupling protein 2 (UCP-2) leads to a rapid and dramatic fall in mitochondrial membrane potential and to a reduction of mitochondrial NADH and intracellular ATP. In HeLa cells, increased UCP-2 expression leads to a form of cell death that is not inhibited by the anti-apoptotic gene product Bcl-2 and that morphologically resembles cellular oncosis. We further describe the creation of a dominant interfering mutant of UCP-2 whose expression increases resting mitochondrial membrane potential and selectively increases the resistance to cell death following oncotic but not apoptotic stimuli. These results suggest that distinct genetic programs may regulate the cellular response to either apoptotic or oncotic stimuli.

Original languageEnglish (US)
Pages (from-to)27385-27392
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number30
DOIs
StatePublished - Jul 26 2002
Externally publishedYes

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Cell death
Cell Death
Mitochondrial Membrane Potential
HeLa Cells
Proteins
Membranes
bcl-2 Genes
Mutant Proteins
Fibroblasts
Diploidy
NAD
Membrane Potentials
Swelling
Genes
Adenosine Triphosphate
Apoptosis
Uncoupling Protein 2

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mills, E. M., Xu, D., Fergusson, M. M., Combs, C. A., Xu, Y., & Finkel, T. (2002). Regulation of cellular oncosis by uncoupling protein 2. Journal of Biological Chemistry, 277(30), 27385-27392. https://doi.org/10.1074/jbc.M111860200

Regulation of cellular oncosis by uncoupling protein 2. / Mills, Edward M.; Xu, Dong; Fergusson, María M.; Combs, Christian A.; Xu, Yuhui; Finkel, Toren.

In: Journal of Biological Chemistry, Vol. 277, No. 30, 26.07.2002, p. 27385-27392.

Research output: Contribution to journalArticle

Mills, EM, Xu, D, Fergusson, MM, Combs, CA, Xu, Y & Finkel, T 2002, 'Regulation of cellular oncosis by uncoupling protein 2', Journal of Biological Chemistry, vol. 277, no. 30, pp. 27385-27392. https://doi.org/10.1074/jbc.M111860200
Mills EM, Xu D, Fergusson MM, Combs CA, Xu Y, Finkel T. Regulation of cellular oncosis by uncoupling protein 2. Journal of Biological Chemistry. 2002 Jul 26;277(30):27385-27392. https://doi.org/10.1074/jbc.M111860200
Mills, Edward M. ; Xu, Dong ; Fergusson, María M. ; Combs, Christian A. ; Xu, Yuhui ; Finkel, Toren. / Regulation of cellular oncosis by uncoupling protein 2. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 30. pp. 27385-27392.
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