FIGURE 7.

A hypothetical model illustrating the involvement of p53, Phb1, Oma1, and Opa1 in the regulation of mitochondrial fragmentation, apoptosis, and chemosensitivity in gynecologic cells. In chemosensitive cells, CDDP induces p53 phosphorylation (serine 15), which translocates to the mitochondria and targets the complex of Phb1 and Opa1 (five forms). Phospho-p53 (serine 15) binds to Phb1 and releases Opa1. CDDP also induces Oma1 activation, which processes L-Opa1 and induces mitochondrial fragmentation and subsequent apoptosis. In chemoresistant cells, CDDP-induced p53 phosphorylation is minimal or inhibited and therefore stabilizes the complex of Phb1 and Opa1 (three forms). CDDP-induced Oma1 activation is also inhibited. L-Opa1 is protected from being processed, leading to the failure of CDDP to induce mitochondrial fragmentation and apoptosis.