Inhibition of apoptotic potency by ligand stimulated thyroid hormone receptors located in mitochondria

Nuttawut Saelim, Deborah Holstein, Estrella S. Chocron, Patricia Camacho, James Donald Lechleiter

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

We recently reported that shortened thyroid hormone receptor isoforms (TRs) can target mitochondria and acutely modulate inositol 1,4,5 trisphosphate (IP3)-mediated Ca2+ signaling when activated by thyroid hormone 3,5,3′-tri-iodothyronine (T3). Stimulation occurs via an increase in mitochondrial metabolism that is independent of transcriptional activity. Here, we present evidence that T3-bound xTR βA1s inhibit apoptotic activity mediated by cytochrome c release. An assay for apoptotic potency was modified to measure the ability of Xenopus oocyte extracts to induce morphological changes in isolated liver nuclei. Apoptotic potency was significantly decreased when oocyte extract was prepared from xTRβA1 expressing oocytes and treated with T 3. The ability of T3 treatment to inhibit apoptosis was dependent on the expression of xTRβA1s in the mitochondrial fraction, not in the cytosolic fraction. T3 treatment also increased the membrane potential of isolated mitochondria prepared from oocytes expressing xTRβA1s but not from wildtype controls. We conclude that T 3 acutely regulates cytochrome c release in a potential dependent manner by activating TRs located within mitochondria.

Original languageEnglish (US)
Pages (from-to)1781-1794
Number of pages14
JournalApoptosis
Volume12
Issue number10
DOIs
StatePublished - Oct 2007

Keywords

  • Apoptosis assay
  • Confocal microscopy
  • Steroid receptors
  • Xenopus oocytes

ASJC Scopus subject areas

  • Biochemistry, medical
  • Cancer Research
  • Clinical Biochemistry
  • Cell Biology
  • Pharmacology
  • Pharmaceutical Science

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