title: CD147 interacts with NDUFS6 in regulating mitochondrial complex I activity and the mitochondrial apoptotic pathway in human malignant melanoma cells.
abstract: Malignant melanoma (MM) is one of the most lethal tumors and is characterized by high invasiveness, frequent metastasis, and resistance to chemotherapy. The risk of metastatic MM is accompanied by disordered energy metabolism involving the oxidative phosphorylation (OXPHOS) process, which is largely carried out in mitochondrial complexes. Complex I is the first and largest mitochondrial enzyme complex associated with this process. CD147 is a transmembrane glycoprotein mainly expressed on the cell surface, and also appears in the cytoplasm in some tumors. We found that CD147 is often translocated to the cytoplasm in metastatic MM specimens as compared to primary MM. We also demonstrated high expression of CD147 in isolated mitochondrial fractions of A375 cells. The yeast two-hybrid (Y2H) assay identified NDUFS6 (which encodes a subunit of mitochondrial respiratory chain complex I) as a candidate that interacts with CD147 and depletion of CD147 in A375 cells significantly decreased complex I enzyme activity. We also showed that CD147 increased the viability of A375 cells exposed to berberine-induced mitochondrial damage, and protected them from apoptosis through a mitochondrial-dependent pathway. This finding was confirmed by adding exogenous Bcl-2 to A375 cell cultures. In summary, our results identify the existence of CD147 in human melanoma cell mitochondria. They indicate that CD147 appears to regulate complex I activity and apoptosis in MM by interacting with mitochondrial NDUFS6. Our findings provide new insight into the function of CD147 and identify it as a promising therapeutic target in melanoma through disruption of the energy metabolism.
authors.forename: Z
authors.initials: Z
authors.lastname: Luo
authors.forename: W
authors.initials: W
authors.lastname: Zeng
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.forename: T
authors.initials: T
authors.lastname: Long
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Xie
authors.forename: Y
authors.initials: Y
authors.lastname: Kuang
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Su
authors.affiliation: (X. Chen) Department of Dermatology, XiangYa Hospital, Central South University, 87 XiangYa Road, Changsha, Hunan 410008, China. chenxiangck@gmail.com.
authors.forename: X
authors.initials: X
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D001599:Berberine / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020798:Two-Hybrid System Techniques
chemical_list: C000595707:BCL2 protein, human; C497886:BSG protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D001599:Berberine; D051926:Basigin; D009245:NADH Dehydrogenase; C493878:NDUFS6 protein, human; D042967:Electron Transport Complex I