Mitochondrial apoptosis is amplified through gap junctions

Pablo M. Peixoto, Shin Young Ryu, Dawn Pietkiewicz Pruzansky, Maria Kuriakose, Andrew Gilmore, Kathleen W. Kinnally

Research output: Contribution to journalArticle

Abstract

The death of one cell can precipitate the death of nearby cells in a process referred to as the bystander effect. We investigated whether mitochondrial apoptosis generated a bystander effect and, if so, by which pathway. Microinjection with cytochrome c mimicked function of the mitochondrial apoptosis-induced channel MAC and caused apoptosis of both target and nearby osteoblasts. This effect was suppressed by inhibiting gap junction intercellular communication. A bystander effect was also observed after exogenous expression of tBid, which facilitates MAC formation and cytochrome c release. Interestingly, in connexin-43 deficient osteoblasts, microinjection of cytochrome c induced apoptosis only in the target cell. These findings indicate that a death signal was generated downstream of MAC function and was transmitted through gap junctions to amplify apoptosis in neighboring cells. This concept may have implications in development of new therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)38-43
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume390
Issue number1
DOIs
StatePublished - Dec 4 2009

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Keywords

  • Bystander effect
  • Cytochrome c
  • Gap junctions
  • MAC
  • Mitochondrial apoptosis
  • tBid

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Peixoto, P. M., Ryu, S. Y., Pruzansky, D. P., Kuriakose, M., Gilmore, A., & Kinnally, K. W. (2009). Mitochondrial apoptosis is amplified through gap junctions. Biochemical and Biophysical Research Communications, 390(1), 38-43. https://doi.org/10.1016/j.bbrc.2009.09.054