Accession Number : AD1050193


Title :   Clinical Significance and Mechanistic Insights into Ovarian Cancer Mitochondrial Dysfunction


Descriptive Note : Technical Report,01 May 2016,30 Apr 2017


Corporate Author : The Pennsylvania State University Hershey United States


Personal Author(s) : Hempel, Nadine ; Shin,Dong H


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1050193.pdf


Report Date : 01 May 2017


Pagination or Media Count : 55


Abstract : Our work addresses the hypothesis that mitochondrial dysfunction plays a role in the etiology and chemoresistance of epithelial ovarian cancers. We are focusing on the role of the fission protein Drp1 in this context. Specifically we discovered that expression of a low molecular weight Drp1 variant is associated with mitochondrial fission/fusion defects. Mass spec and RNA sequencing analysis has revealed that the low molecular weight (LMW) isoform of Drp1 does not arise as a consequence of alternate transcriptional promoter use, but may be dependent on an alternate variable domain and C-terminal truncation. We are interrogating the role of short Drp1 as a dominant negative fission protein and are investigating its binding affinity to mitochondria and interaction with fission accessory proteins. Investigations on the function of this protein in mediating mitochondrial dysfunction and chemoresistance are ongoing. We have identified that expression of LMW Drp1 is detected in the majority of high grade serous ovarian cancer cells isolated from patient ascites, and that this is associated with hyperfused mitochondria, indicating that this is a clinically relevant observation that could affect a majority of ovarian cancer cases.


Descriptors :   mitochondria , ovarian cancer , proteins , molecular weight


Subject Categories : Medicine and Medical Research
      Biochemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE