Fig. 8

Hypothetical model illustrating in the regulation of mitochondrial fragmentation, apoptosis, and chemosensitivity in gynecologic cancer cells. In chemosensitive cells, 1) CDDP induces p53 phosphorylation (ser15), which accumulates in the mitochondria. 2) p-p53 (ser15) binds to Phb1. 3) The p-p53 (ser15)-Phb1 complex binds to Bak, inducing Bak activation. 4) The p-p53 (ser15)-Phb1-Bak complex activates Oma1 and 5) induces L-Opa1 processing to short form of Opa1. 6) This induces mitochondrial fragmentation in IMM, and subsequent apoptosis. In chemoresistant cells, 1) CDDP-induced p53 phosphorylation is minimal or absence, 2) suppressed stabilizing the Phb1-P-p53 (ser15) complex and 3) attenuatess the association of p-p53 (ser15)-Phb1-Bak complex. 4) It inhibits Oma1 activation in OMM. 5) L-Opa1 is protected from being processed in IMM, leading to the failure of CDDP to induce mitochondrial fragmentation and apoptosis. Solid arrow indicates activation and dashed arrow indicates suppressed activation. OMM and IMM indicate outer membrane inner membrane of mitochondria, respectively