Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3

TR3, an immediate-early response gene and an orphan member of the steroid-t hyroid hormone-retinoid receptor superfamily of transcription factors, regu lates apoptosis through an unknown mechanism. In response to apoptotic stim uli, TR3 translocates from the nucleus to mitochondria to induce cytochrome c release and apoptosis. Mitochondrial targeting of TR3, but not its DNA b inding and transactivation, is essential for its proapoptotic effect. Our r esults reveal a mechanism by which a nuclear transcription factor transloca tes to mitochondria to initiate apoptosis.