Mitochondrial functions and estrogen receptor-dependent nuclear translocation of pleiotropic human prohibitin 2.
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 alpha 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.
Kasashima
Katsumi
K
Department of Biochemistry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Ohta
Eriko
E
Kagawa
Yasuo
Y
Endo
Hitoshi
H
D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing; D000838:Anions / Q000737:chemistry; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D000091402:Prohibitins; D011506:Proteins / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D000838:Anions; D047628:Estrogen Receptor alpha; D004967:Estrogens; C104759:HAX1 protein, human; C000717328:PHB protein, human; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011506:Proteins; D011960:Receptors, Estrogen; D012097:Repressor Proteins; D004958:Estradiol