Mitochondria are highly dynamic organelles, and mitochondrial fission is a 
crucial step of apoptosis. Although Oma1 is believed to be responsible for long 
form Opa1 (L-Opa1) processing during mitochondrial fragmentation, whether and 
how Oma1 is involved in L-Opa1 processing and participates in the regulation of 
chemoresistance is unknown. Chemosensitive and chemoresistant ovarian (OVCA) and 
cervical (CECA) cancer cells were treated with cisplatin (CDDP). Mitochondrial 
dynamics and protein contents were assessed by immunofluorescence and Western 
blot, respectively. The requirements of Oma1 and p53 for CDDP-induced L-Opa1 
processing, mitochondrial fragmentation, and apoptosis were examined by siRNA or 
cDNA. CDDP induces L-Opa1 processing and mitochondrial fragmentation in 
chemosensitive but not in chemoresistant cells. CDDP induced Oma1 40-kDa form 
increases in OV2008 cells, not in C13* cells. Oma1 knockdown inhibited L-Opa1 
processing, mitochondrial fragmentation, and apoptosis. Silencing p53 expression 
attenuated the effects of CDDP in Oma1 (40 kDa) increase, L-Opa1 processing, 
mitochondrial fragmentation, and apoptosis in chemosensitive OVCA cells, whereas 
reconstitution of p53 in p53 mutant or null chemoresistant OVCA cells induced 
Oma1 (40 kDa) increase, L-Opa1 processing, mitochondrial fragmentation, and 
apoptosis irrespective of the presence of CDDP. Prohibitin 1 (Phb1) dissociates 
from Opa1-Phb1 complex and binds phosphorylated p53 (serine 15) in response to 
CDDP in chemosensitive but not chemoresistant CECA cells. These findings 
demonstrate that (a) p53 and Oma1 mediate L-Opa1 processing, (b) mitochondrial 
fragmentation is involved in CDDP-induced apoptosis in OVCA and CECA cells, and 
(c) dysregulated mitochondrial dynamics may in part be involved in the 
pathophysiology of CDDP resistance.