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. 2019 Aug 22;11(16):6449-6468.
doi: 10.18632/aging.102199. Epub 2019 Aug 22.

Quantitative analysis of the human ovarian carcinoma mitochondrial phosphoproteome

Na Li  1   2   3 , Shehua Qian  1   2   3 , Biao Li  1   2   3 , Xianquan Zhan  1   2   3   4
Affiliations

Quantitative analysis of the human ovarian carcinoma mitochondrial phosphoproteome

Na Li et al. Aging (Albany NY). .

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.

Keywords: Mitochondria; Ovarian cancer; TiO enrichment 2; iTRAQ quantitative proteomics; mitochondrial phosphoprotein (mtPP).

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Experimental flow-chart to identify mtPPs, including 18 previously identified mtPPs.
Figure 2
Figure 2
Representative MS/MS spectra of phosphopeptides. (A) 2ADELS*EK8 ([M + 2H]2+, m/z = 609.28284, S* = phosphorylated serine residue) derived from CAV1 (Swiss-Prot No.: C9JKI3). (B) 2AS*GVAVSDGVIK13 ([M + 2H]2+, m/z = 764.89862, S* = phosphorylated serine residue) derived from CFL1 (Swiss-Prot No.: E9PS23). (C) 419KAEDS*DS*EPEPEDNVR434 ([M + 3H]3+, m/z = 862.37878, S* = phosphorylated serine residue) derived from XRN2 (Swiss-Prot No.: B4E0B9).
Figure 3
Figure 3
GO analysis revealed biological processes (BPs; A), cellular components (CCs; B), and molecular functions (MFs; C) that involveds in mtPPs.
Figure 4
Figure 4
Protein-protein interaction network (A) and statistically significant signaling pathways (B) involved in mtPPs.
Figure 5
Figure 5
Identification of phosphorylated sites and protein domains in mtPPs.
Figure 6
Figure 6
Upstream regulation analysis revealed the upstream regulators of mtPPs. Note: The solid line means direct interaction. The dotted line means indirect interaction. The arrow line means activation. The non-arrow line means inactivation. The red molecule means increased measurement. The green molecule means decreased measurement.
See this image and copyright information in PMC

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