Clinical Significance and Mechanistic Insights into Ovarian Cancer Mitochondrial Dysfunction
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2017
- Accession Number
- AD1050193
Entities
People
- Dong Hoon Shin
- Nadine Hempel
Organizations
- Pennsylvania State University