Differential regulation of nuclear and mitochondrial Bcl-2 in T cell apoptosis

Dagmar Scheel-Toellner, Karim Raza, L Assi, Darrell Pilling, Emma Ross, Wing-Yiu Lee, Stephen Curnow, Christopher Buckley, AN Akbar, Janet Lord, Michael Salmon

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Activated T cells require anti-apoptotic cytokines for their survival. The anti-apoptotic effects of these factors are mediated by their influence on the balance of expression and localisation of pro- and anti-apoptotic members of the Bcl-2 family. Among the anti-apoptotic Bcl-2 family members, the expression level of Bcl-2 itself and its interaction with the pro-apoptotic protein Bim are now regarded as crucial for the regulation of survival in activated T cells. We studied the changes in Bcl-2 levels and its subcellular distribution in relation to mitochondrial depolarisation and caspase activation in survival factor deprived T cells. Intriguingly, the total Bcl-2 level appeared to remain stable, even after caspase 3 activation indicated entry into the execution phase of apoptosis. However, cell fractionation experiments showed that while the dominant nuclear pool of Bcl-2 remained stable during apoptosis, the level of the smaller mitochondrial pool was rapidly downregulated. Signals induced by anti-apoptotic cytokines continuously replenish the mitochondrial pool, but nuclear Bcl-2 is independent of such signals. Mitochondrial Bcl-2 is lost rapidly by a caspase independent mechanism in the absence of survival factors, in contrast only a small proportion of the nuclear pool of Bcl-2 is lost during the execution phase and this loss is a caspase dependent process. We conclude that these two intracellular pools of Bcl-2 are regulated through different mechanisms and only the cytokine-mediated regulation of the mitochondrial pool is relevant to the control of the initiation of apoptosis.
Original languageEnglish
Pages (from-to)109-17
Number of pages9
Issue number1
Early online date23 Oct 2007
Publication statusPublished - 1 Jan 2008


  • cytokines
  • lymphocytes
  • programmed cell death
  • Bcl-2
  • survival


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