Mitochondrial Functions and Estrogen Receptor-dependent Nuclear Translocation of Pleiotropic Human Prohibitin 2

• Published in: The Journal of biological chemistry 2006-11, Vol.281 (47), p.36401-36410
• Main Authors: Kasashima, Katsumi, Ohta, Eriko, Kagawa, Yasuo, Endo, Hitoshi
• Format: Article
• Language: English
• Subjects: Active Transport, Cell Nucleus; Adaptor Proteins, Signal Transducing; Anions - chemistry; Cell Line, Tumor; Cell Nucleus - metabolism; Estradiol - metabolism; Estrogen Receptor alpha - metabolism; Estrogens - metabolism; Fibroblasts - metabolism; HeLa Cells; Humans; Mitochondria - metabolism; Models, Biological; Proteins - metabolism; Receptors, Estrogen - metabolism; Repressor Proteins - chemistry; Repressor Proteins - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M605260200

Proteins with multiple cellular functions provide biological diversity to eukaryotic cells. In the current studies, we identified the mitochondrial functions of human prohibitin 2 (PHB2), which was initially identified as a repressor of estrogen-dependent transcriptional activity. The mitochondrial complex of PHB2 consists of PHB1, voltage-dependent anion channel 2, adenine nucleotide translocator 2, and the anti-apoptotic Hax-1, which is a novel binding partner for PHB2. RNA interference-mediated knockdown of PHB2 in HeLa cells resulted in caspase-dependent apoptosis through down-regulation of Hax-1 and fragmentation of mitochondria. We also found that, although PHB2 is predominantly expressed in the mitochondria of HeLa cells, it translocates to nucleus in the presence of estrogen receptor α and estradiol. Here, we first demonstrated the roles of mammalian PHB2 in mitochondria and the molecular mechanism of its nuclear targeting and showed that PHB2 is a possible molecule directly coupling nuclear-mitochondrial interaction.