Mass Spectrometry‐based Mitochondrial Proteomics in Human Ovarian Cancers

Abstract

The prominent characteristics of mitochondria are highly dynamic and regulatory, which have crucial roles in cell metabolism, biosynthetic, senescence, apoptosis, and signaling pathways. Mitochondrial dysfunction might lead to multiple serious diseases, including cancer. Therefore, identification of mitochondrial proteins in cancer could provide a global view of tumorigenesis and progression. Mass spectrometry‐based quantitative mitochondrial proteomics fulfils this task by enabling systems‐wide, accurate, and quantitative analysis of mitochondrial protein abundance, and mitochondrial protein posttranslational modifications (PTMs). Multiple quantitative proteomics techniques, including isotope‐coded affinity tag, stable isotope labeling with amino acids in cell culture, isobaric tags for relative and absolute quantification, tandem mass tags, and label‐free quantification, in combination with different PTM‐peptide enrichment methods such as TiO2 enrichment of tryptic phosphopeptides and antibody enrichment of other PTM‐peptides, increase flexibility for researchers to study mitochondrial proteomes. This article reviews isolation and purification of mitochondria, quantitative mitochondrial proteomics, quantitative mitochondrial phosphoproteomics, mitochondrial protein‐involved signaling pathway networks, mitochondrial phosphoprotein‐involved signaling pathway networks, integration of mitochondrial proteomic and phosphoproteomic data with whole tissue proteomic and transcriptomic data and clinical information in ovarian cancers (OC) to in‐depth understand its molecular mechanisms, and discover effective mitochondrial biomarkers and therapeutic targets for predictive, preventive, and personalized treatment of OC. This proof‐of‐principle model about OC mitochondrial proteomics is easily implementable to other cancer types. © 2020 John Wiley & Sons Ltd. Mass Spec Rev

SILAC quantitative proteomics analysis of ivermectin‐related proteomic profiling and molecular network alterations in human ovarian cancer cells

“…Ovarian cancer is the leading cause of death from gynecologic cancer, and the 5‐year overall survival rate remains poor (about 30%) for patients diagnosed with stages III and IV ovarian cancer 8,23,36 . Ivermectin has been reported to augment the efficacy of cisplatin in the treatment of ovarian cancer by suppressing Akt/mTOR signaling 10 .…”

“…for patients diagnosed with stages III and IV ovarian cancer. 8,23,36 Ivermectin has been reported to augment the efficacy of cisplatin in the treatment of ovarian cancer by suppressing Akt/mTOR signaling. 10 However, the role and mechanism of ivermectin in inhibiting ovarian cancer remain unclear.…”

“…Drug repositioning is one of the most effective alternative strategies to develop new anticancer drugs because of existing compounds and confirmed clinical safety 7 . Ovarian cancer is one of the most common cancers and the most common cause of mortality in women 8 . Although a more reasonable, standard, and effective therapy has been established for ovarian cancer, cancer survival rate remains poor 9 .…”

“…7 Ovarian cancer is one of the most common cancers and the most common cause of mortality in women. 8 Although a more reasonable, standard, and effective therapy has been established for ovarian cancer, cancer survival rate remains poor. 9 One study suggests that ivermectin might be a potential addition to the treatment for ovarian cancer through targeting Akt/mTOR signaling to increase chemosensitivity in ovarian cancer.…”

The Anti-Cancer Effects of Anti-Parasite Drug Ivermectin in Ovarian Cancer

“…Ovarian cancer, a very common cancer with high mortality and poor survival in women [9,10], are involved in multiple signaling pathway network changes [11,12]. Many intracellular molecules and signaling pathways would be the targets of ivermectin [13].…”