Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria (Genes & Dev, 2008, 22:476-488)

報告日期: 2008/12/09
報告時間: 15:10/16:00
報告學生: 鄭蕙芬(英文報告)
講評老師: 蔣輯武
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971209-1.pdf

Prohibitins control cell proliferation and apoptosis by regulating OPA1- dependent cristae morphogenesis in mitochondria

Gene & development (2008), 22: 476-488

Speaker: Huei-Fen Jheng

Commentator: Dr. Chi-Wu Chiang

Date: 12/09/2008

Place: 602 room

 

The prohibitins, PHB1 and PHB2, are highly conserved proteins in eukaryotic cells and ubiquitously expressed in multiple cellular compartments such as mitochondria, nucleus and plasma membrane. Although previous studies suggested that the PHBs were involved in the regulation of cell cycle and apoptosis, they did not dissect the role of mitochondria-localized PHBs. In addition, since PHB1 and PHB2 have been demonstrated to assemble with each other, it is intriguing to study both PHB1 and PHB2 proteins together. The authors used conditional gene targeting of Phb2 in mouse embryonic fibroblast (MEF). They found that the deletion of Phb2 resulted in loss of both PHB1 and PHB2 proteins, indicating that PHB1 and PHB2 are interdependent. In PHB2-deleted MEF, incorporation of 3H-thymidine and cell growth were impaired, and the response to apoptotic stimuli was increased. These impairments were rescued after transfection of intact PHB2, but not defective mitochondria-targeted PHB2. Furthermore, the results revealed that deletion of Phb2 resulted in the selective loss of long isoform of OPA1, an essential component of mitochondrial fusion machinery, along with an aberrant cristae morphogenesis; while other factors reported to affect OPA1 processing and mitochondrial fragmentation, such as membrane potential and respiratory activity, were not changed in PHB2-deleted cell. These results suggested that the accelerated processing of OPA1 in PHB2-deficient cell was caused by other factors. Moreover, expression of a long OPA1 isoform in PHB2-deficient cell restored normal cristae morphology, the apoptotic resistance and cell proliferation. Taken together, these results indicated an essential function for the formation of mitochondrial cristae to PHBs and suggested a coupling of cell proliferation to mitochondrial morphogenesis.

 

Reference:

1.    Mishra, S., Murphy, L.C., Nyomba, B.L.G., and Murphy, L.J.2005. Prohibitin: A potential target for new therapeutics. Trends Mol. Med. 11: 192–197.

2.    Mishra, S., Murphy, L.C., and Murphy, L.J.2006. The prohibitins: emerging roles in diverse functions. J. Cell.Mol.Med. 2: 353-363

3.    Chan, D.C. 2006. Mitochondrial fusion and fission in mammals. Annu Rev.Cell Dev. Biol. 22: 79-99