Abstract
To investigate the existence and their potential biological roles of mitochondrial phosphoproteins (mtPPs) in human ovarian carcinoma (OC), mitochondria purified from OC and control tissues were analyzed with TiO2 enrichment-based iTRAQ quantitative proteomics. Totally 67 mtPPs with 124 phosphorylation sites were identified, which of them included 48 differential mtPPs (mtDPPs). Eighteen mtPPs were reported previously in OCs, and they were consistent in this study compared to previous literature. GO analysis revealed those mtPPs were involved in multiple cellular processes. PPI network indicated that those mtPPs were correlated mutually, and some mtPPs acted as hub molecules, such as EIF2S2, RPLP0, RPLP2, CFL1, MYH10, HSP90, HSPD1, PSMA3, TMX1, VDAC2, VDAC3, TOMM22, and TOMM20. Totally 32 mtPP-pathway systems (p<0.05) were enriched and clustered into 15 groups, including mitophagy, apoptosis, deubiquitination, signaling by VEGF, RHO-GTPase effectors, mitochondrial protein import, translation initiation, RNA transport, cellular responses to stress, and c-MYC transcriptional activation. Totally 29 mtPPs contained a certain protein domains. Upstream regulation analysis showed that TP53, TGFB1, dexamethasone, and thapsigargin might act as inhibitors, and L-dopa and forskolin might act as activators. This study provided novel insights into mitochondrial protein phosphorylations and their potential roles in OC pathogenesis and offered new biomarker resource for OCs.
Highlights
The completion of human genome sequencing has identified about 20,300 human genes [1]
A total of 67 mitochondrial phosphoproteins (mtPPs) based on 85 phosphopeptides with 124 phosphorylation sites were identified in the control and ovarian carcinoma (OC) samples with iTRAQ-TiO2 enrichment-LCMS/MS between OC mitochondria relative to controls (Supplementary Table 3); and among them, 48 differentially phosphorylated proteins were identified between OC and control samples
The phosphorylation site was localized to amino acid residue S*3, and the phosphorylation level was significantly decreased in OCs compared to controls (Supplementary Table 3)
Summary
The completion of human genome sequencing has identified about 20,300 human genes [1]. Researchers are always expecting to clarify molecular mechanisms of a human disease at the level of genome [2]. Variations at the levels of DNAs, RNAs, and proteins lead to proteome diversity; and those variations are commonly derived from mutations, splicing, and posttranslational modifications (PTMs) [3]. There are about 400-600 PTMs in human body, such as phosphorylation, acetylation, nitration, ubiquitylation, and glycosylation, which is one of main reasons to cause the diversity of proteins, and influences protein structures and functions [4]. High mortality rate is still an important clinical challenge in ovarian carcinoma (OC) patients. It is www.aging-us.com necessary to develop new reliable biomarkers and effective therapies for OC patients, which has been driven by proteomics [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
