Mitochondrial Oxidative Phosphorylation Complex Regulates NLRP3 Inflammasome Activation and Predicts Patient Survival in Nasopharyngeal Carcinoma

We previously reported that tumor inflammasomes play a key role in tumor control and act as favorable prognostic markers in nasopharyngeal carcinoma (NPC). Activated inflammasomes frequently form distinguishable specks and govern the cellular secretion of IL-1β. However, we know little about the biological and biochemical differences between cells with and without apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) speck formation. In this study, we used proteomic iTRAQ analysis to analyze the proteomes of NPC cells that differ in their ASC speck formation upon cisplatin treatment. We identified proteins that were differentially over-expressed in cells with specks, and found that they fell into two Gene ontology (GO) pathways: mitochondrial oxidative phosphorylation (OxPhos) and ubiquinone metabolism. We observed up-regulation of various components of the OxPhos machinery (including NDUFB3, NDUFB8 and ATP5B), and subsequently found that these changes lead to mitochondrial ROS (mtROS) production, which promotes the formation and activation of NLRP3 inflammasomes and subsequent pyroptosis. In NPC patients, better local recurrence-free survival was significantly associated with high-level expression of NDUFB8 (p = 0.037) and ATP5B (p = 0.029), as examined using immunohistochemistry. However, there were no significant associations between the expression of NDUFB8 and ATP5B with overall survival of NPC patients. Together, our results demonstrate that up-regulated mitochondrial OxPhos components are strongly associated with NLRP3 inflammasome activation in NPC. Our findings further suggest that high-level expression of OxPhos components could be markers for local recurrence and/or promising therapeutic targets in patients with NPC. We previously reported that tumor inflammasomes play a key role in tumor control and act as favorable prognostic markers in nasopharyngeal carcinoma (NPC). Activated inflammasomes frequently form distinguishable specks and govern the cellular secretion of IL-1β. However, we know little about the biological and biochemical differences between cells with and without apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) speck formation. In this study, we used proteomic iTRAQ analysis to analyze the proteomes of NPC cells that differ in their ASC speck formation upon cisplatin treatment. We identified proteins that were differentially over-expressed in cells with specks, and found that they fell into two Gene ontology (GO) pathways: mitochondrial oxidative phosphorylation (OxPhos) and ubiquinone metabolism. We observed up-regulation of various components of the OxPhos machinery (including NDUFB3, NDUFB8 and ATP5B), and subsequently found that these changes lead to mitochondrial ROS (mtROS) production, which promotes the formation and activation of NLRP3 inflammasomes and subsequent pyroptosis. In NPC patients, better local recurrence-free survival was significantly associated with high-level expression of NDUFB8 (p = 0.037) and ATP5B (p = 0.029), as examined using immunohistochemistry. However, there were no significant associations between the expression of NDUFB8 and ATP5B with overall survival of NPC patients. Together, our results demonstrate that up-regulated mitochondrial OxPhos components are strongly associated with NLRP3 inflammasome activation in NPC. Our findings further suggest that high-level expression of OxPhos components could be markers for local recurrence and/or promising therapeutic targets in patients with NPC. Inflammation plays important roles at different stages of tumorigenesis. A key signal involved in driving acute and chronic inflammation is controlled by the inflammasome, which is an inducible cytoplasmic multiprotein complex that serves as a platform for sensing danger signals in the tumor microenvironment (1He Q. Fu Y. Tian D. Yan W. The contrasting roles of inflammasomes in cancer.Am. J. Cancer Res. 2018; 8: 566-583PubMed Google Scholar, 2Moossavi M. Parsamanesh N. Bahrami A. Atkin S.L. Sahebkar A. Role of the NLRP3 inflammasome in cancer.Mol. Cancer. 2018; 17: 158Crossref PubMed Scopus (226) Google Scholar). Various inflammasomes have been identified. Some comprise intracellular pattern recognition receptors, such as nod-like receptors and AIM2-like receptors, which can be activated by pathogen-associated molecule patterns and damage-associated molecule patterns (3Awad F. Assrawi E. Louvrier C. Jumeau C. Georgin-Lavialle S. Grateau G. Amselem S. Giurgea I. Karabina S.A. Inflammasome biology, molecular pathology and therapeutic implications.Pharmacol. Therapeutics. 2018; 187: 133-149Crossref PubMed Scopus (75) Google Scholar). The apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) 1The abbreviations used are:ASCapoptosis-associated speck-like protein containing a caspase-recruitment domainCIDcollision-induced dissociationsEB1end-binding protein 1EBVEpstein-Barr virusETCelectron transport chainFLICAfluorochrome labeled inhibitors of caspase-1GOGene ontologyHCDhigher-energy collision-induced dissociationsIHCimmunohistochemistryIRBInstitutional Review BoardLDHlactate dehydrogenaseLMP1latent membrane protein 1MAVSmitochondrial antiviral signaling proteinMfn2mitofusin 2mtDNAmitochondrial DNAmtΔΨmitochondrial membrane potentialmtROSmitochondrial reactive oxygen speciesNPCnasopharyngeal carcinomaOxPhosoxidative phosphorylationPIpropidium iodidePYCARDPYD and CARD domain containingSDstandard deviationTEABCtriethylammonium bicarbonateTFAtrifluoroacetic acid. 1The abbreviations used are:ASCapoptosis-associated speck-like protein containing a caspase-recruitment domainCIDcollision-induced dissociationsEB1end-binding protein 1EBVEpstein-Barr virusETCelectron transport chainFLICAfluorochrome labeled inhibitors of caspase-1GOGene ontologyHCDhigher-energy collision-induced dissociationsIHCimmunohistochemistryIRBInstitutional Review BoardLDHlactate dehydrogenaseLMP1latent membrane protein 1MAVSmitochondrial antiviral signaling proteinMfn2mitofusin 2mtDNAmitochondrial DNAmtΔΨmitochondrial membrane potentialmtROSmitochondrial reactive oxygen speciesNPCnasopharyngeal carcinomaOxPhosoxidative phosphorylationPIpropidium iodidePYCARDPYD and CARD domain containingSDstandard deviationTEABCtriethylammonium bicarbonateTFAtrifluoroacetic acid. protein, also called PYD and CARD domain containing (PYCARD), is encoded by PYCARD gene in human and is a key component of all known inflammasomes. Upon initiation of inflammasome activation, all inflammasomes recruit the adaptor protein ASC assembles into a large helical fibril called the ASC speck (4Hoss F. Rodriguez-Alcazar J.F. Latz E. Assembly and regulation of ASC specks.Cell. Mol. Life Sci. 2017; 74: 1211-1229Crossref PubMed Scopus (68) Google Scholar). The ASC speck serves as signaling platform for caspase-1, leading to the activation of caspase-1, the maturation of pro-inflammatory cytokines (e.g. IL-1β) and the initiation of a lytic form of programmed cell death known as pyroptosis (5Kovacs S.B. Miao E.A. Gasdermins: effectors of pyroptosis.Trends Cell Biol. 2017; 27: 673-684Abstract Full Text Full Text PDF PubMed Scopus (531) Google Scholar). apoptosis-associated speck-like protein containing a caspase-recruitment domain collision-induced dissociations end-binding protein 1 Epstein-Barr virus electron transport chain fluorochrome labeled inhibitors of caspase-1 Gene ontology higher-energy collision-induced dissociations immunohistochemistry Institutional Review Board lactate dehydrogenase latent membrane protein 1 mitochondrial antiviral signaling protein mitofusin 2 mitochondrial DNA mitochondrial membrane potential mitochondrial reactive oxygen species nasopharyngeal carcinoma oxidative phosphorylation propidium iodide PYD and CARD domain containing standard deviation triethylammonium bicarbonate trifluoroacetic acid. apoptosis-associated speck-like protein containing a caspase-recruitment domain collision-induced dissociations end-binding protein 1 Epstein-Barr virus electron transport chain fluorochrome labeled inhibitors of caspase-1 Gene ontology higher-energy collision-induced dissociations immunohistochemistry Institutional Review Board lactate dehydrogenase latent membrane protein 1 mitochondrial antiviral signaling protein mitofusin 2 mitochondrial DNA mitochondrial membrane potential mitochondrial reactive oxygen species nasopharyngeal carcinoma oxidative phosphorylation propidium iodide PYD and CARD domain containing standard deviation triethylammonium bicarbonate trifluoroacetic acid. Nasopharyngeal carcinoma (NPC) is a cancer that is prominent in the Taiwanese population. It is closely associated with Epstein-Barr virus (EBV) infection. In tumor cells, EBV-encoded latent membrane protein 1 (LMP1) mediates pro-IL-1β gene expression through NF-κB signaling (6Chen L.C. Wang L.J. Tsang N.M. Ojcius D.M. Chen C.C. C. Y. Chen C.C. and local recurrence-free survival in nasopharyngeal Mol. PubMed Scopus Google Scholar). the NPC tumor tumor the of are Chen J. Y. Chen of expression in nasopharyngeal a expression of 1 in tumor and Res. Google Scholar). of and the and inflammasomes were reported to be as prognostic for better recurrence-free survival of NPC patients with the (6Chen L.C. Wang L.J. Tsang N.M. Ojcius D.M. Chen C.C. C. Y. Chen C.C. and local recurrence-free survival in nasopharyngeal Mol. PubMed Scopus Google Scholar). protein 1 which was reported to with ASC of the and inflammasomes in NPC cells and was found to be for speck formation in to inflammasome activation L.J. Chen C.C. Y. Chen L.C. Ojcius D.M. Tsang N.M. C. C.C. analysis end-binding protein 1 as a component for the speck-like formation of activated in 2 Full Text Full Text PDF PubMed Scopus Google Scholar). also been to the secretion of and the and secretion of was found to be by activated protein L.J. W. C.C. Ojcius D.M. The protein inflammasomes with Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). found that the NLRP3 inflammasome is activated by and the in NPC cells (6Chen L.C. Wang L.J. Tsang N.M. Ojcius D.M. Chen C.C. C. Y. Chen C.C. and local recurrence-free survival in nasopharyngeal Mol. PubMed Scopus Google Scholar, S.B. J. Chen J. J. cell in nasopharyngeal 2017; PubMed Scopus Google Scholar). However, we know little about the changes in cellular components of activated inflammasomes. that act as the of the they also as signaling that can signal to and in the regulation of and Full Text Full Text PDF PubMed Scopus Google Scholar). have that mitochondrial NLRP3 inflammasome activation Q. D. D. Y. The role of in NLRP3 inflammasome 2018; PubMed Scopus Google Scholar). NLRP3 inflammasome activation various that can be mitochondrial such as mitochondrial membrane potential A. E. S. S. J. F. D. G. E. J. M. inflammasome activation of Full Text Full Text PDF PubMed Scopus Google mitochondrial membrane signaling and mitochondrial in the of the NLRP3 Full Text Full Text PDF PubMed Scopus Google and the of mitochondrial ROS (mtROS) J. A role for in NLRP3 inflammasome PubMed Scopus Google of mitochondrial DNA S. E. F. S. J. S. E. M. mitochondrial DNA NLRP3 inflammasome 2018; PubMed Scopus Google and Q. S.L. is for inflammasome Full Text Full Text PDF PubMed Scopus Google and mitochondrial antiviral signaling protein N. Wang The adaptor promotes NLRP3 mitochondrial and inflammasome Full Text Full Text PDF PubMed Scopus Google and mitofusin 2 Y. protein mitofusin 2 is for NLRP3 inflammasome activation virus Sci. PubMed Scopus Google and NLRP3 to mitochondrial membrane and NLRP3 inflammasome can leading to further NLRP3 inflammasome The electron transport chain is in the mitochondrial It is the of oxidative phosphorylation (OxPhos) and is involved in the of oxygen as an electron and and by and the are used to the are the membrane of to the of mitochondrial potential been associated with the of J. A role for in NLRP3 inflammasome PubMed Scopus Google and changes in cellular M. The membrane complex intracellular leading to NLRP3 inflammasome Cell Sci. PubMed Scopus Google in the of NLRP3 inflammasome are the of cellular ROS are the of 2017; PubMed Scopus Google Scholar). of the that NLRP3 inflammasome formation and inhibitors of OxPhos production, which can lead to NLRP3 inflammasome activation J. A role for in NLRP3 inflammasome PubMed Scopus Google Scholar). we previously that the mitochondrial and by NLRP3 inflammasome activation Chen Ojcius D.M. Chen L.C. NLRP3 inflammasome 2018; PubMed Scopus Google Scholar). Together, the results that can be an for NLRP3 inflammasome we that mitochondrial OxPhos components are in ASC NPC cells and are to in NLRP3 inflammasome activation and cell pyroptosis. the components of OxPhos are in tumor cells and significantly with better survival of NPC patients. Our findings further the molecular of NLRP3 inflammasome activation and suggest that OxPhos proteins could as favorable markers for local recurrence in NPC patients. NPC cell and an NPC cell were by S. W. and as previously (6Chen L.C. Wang L.J. Tsang N.M. Ojcius D.M. Chen C.C. C. Y. Chen C.C. and local recurrence-free survival in nasopharyngeal Mol. PubMed Scopus Google Scholar, Epstein-Barr virus cellular signal in human nasopharyngeal 8: PubMed Scopus Google Scholar). The cell was a of a Taiwanese with NPC and as previously Wang of a nasopharyngeal carcinoma cell a Full Text Full Text PDF PubMed Scopus Google Scholar). of and cells, the and cells were with containing an using a inflammasome activation, the cells were with cisplatin the cells were with for 1 and cells were with cisplatin for and ASC and cells were by as previously Chen Ojcius D.M. Chen L.C. NLRP3 inflammasome 2018; PubMed Scopus Google Scholar, N. 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The secretion of was significantly in cells with NLRP3 in been reported to with the cells were also for the inflammasome activation with NLRP3 secretion were we used NPC cells in The of speck cells were in cells with cisplatin to to to to to that NLRP3 inflammasome is by the domain of proteins to the which results in the formation of speck-like A. J. Q. for the of Full Text Full Text PDF PubMed Scopus Google Scholar). However, the molecular involved in speck formation and inflammasome activation this we cells an protein to as The cells to ASC speck formation in to with the various NLRP3 a significant of secretion were in cells with NLRP3 cells with cisplatin which is used to NPC of ASC speck formation NLRP3 for nasopharyngeal carcinoma and Full Text Full Text PDF PubMed Scopus Google in and the proteomic differences between the and cells, we these cell by N. Chen A to inflammasome PubMed Scopus Google and to proteomic analysis The analysis in and proteins which were identified and A of proteins were found to be in cells cisplatin and that of the proteins in the cells were involved in mitochondrial and results that mitochondrial proteins play roles in NLRP3 inflammasome activation in NPC Gene ontology (GO) analysis of the proteins found to be in NPC cells that of in two biological pathways: mitochondrial OxPhos (p = and ubiquinone (p = We also observed that the of OxPhos proteins were in ASC cells the proteins found to be significantly in ASC cells were all of the OxPhos with to and We proteins iTRAQ cells ASC were at the in two biological and to further using In ASC cells, we of complex and complex and complex and cells, NPC cell which secretion and ASC speck formation in to cisplatin were also used to the in protein between and cells through proteomic analysis The analysis in and proteins which were identified and A of proteins were found to be in cells cisplatin the results that mitochondrial OxPhos components are in ASC cells and strongly that mitochondrial OxPhos components play a role in NLRP3 inflammasome formation and activation in NPC proteins were in cells ATP5B and were further by cells with and further with in the of cells was significantly in cells with NDUFB3, NDUFB8 and We used the which a with the J. 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PubMed Scopus Google Scholar). in the of activated cells was significantly in cells with control cells inflammasome these cells to the control results were in cells our results that the mitochondrial OxPhos NDUFB3, NDUFB8 and to be involved in inflammasome activation and play important roles in cell pyroptosis. the results strongly that the mitochondrial OxPhos proteins are involved in NLRP3 inflammasome activation, the to NLRP3 inflammasome activation in NPC cells have that the NLRP3 inflammasome is activated by M. Y. regulation of NLRP3 ROS as PubMed Scopus Google Scholar, A. A. as a in the 2017; Scopus Google the mitochondrial OxPhos machinery is the of production, and mitochondrial to M. reactive oxygen species and ROS PubMed Scopus Google Scholar). we examined the of NDUFB3, and ATP5B the by NLRP3 inflammasome Our that the of were in ASC and cells as with ASC and that caspase-1 activation and cell death were significantly by with the and NPC cells significant in Together, these suggest that is an of NLRP3 inflammasome activation in NPC cells, and that mitochondrial OxPhos proteins in these We previously reported that of inflammasome protein components (e.g. are significantly with better recurrence-free survival of NPC patients (6Chen L.C. Wang L.J. Tsang N.M. Ojcius D.M. Chen C.C. C. Y. Chen C.C. and local recurrence-free survival in nasopharyngeal Mol. PubMed Scopus Google Scholar). In the study, we that OxPhos proteins are involved in NLRP3 inflammasome activation and cell death in NPC these inflammasome OxPhos proteins are associated with we examined NPC patients a of We analysis to the expression of NDUFB8 and ATP5B in We used the expression of NDUFB8 two in and ATP5B two in to the NPC tumor into and the of with survival that better local recurrence-free survival was NPC patients in the for NDUFB8 (p = in and ATP5B (p = in our results that NDUFB8 and ATP5B can NLRP3 inflammasome activation and cell we their expression were and there was prognostic in the expression of these we found that the expression of NDUFB8 and was with that of ATP5B in NPC and that high-level expression of NDUFB8 and ATP5B in the tumor was strongly associated with better local recurrence-free survival of patients (p = We a analysis of NDUFB8 and ATP5B expression with tumor and and found that expression (p = was a of better local recurrence-free survival expression was an of better local recurrence-free survival in analysis (p expression of NDUFB8 and ATP5B as for better local recurrence-free survival (p = However, survival and analysis no significant between the expression of NDUFB8 and ATP5B with overall survival of NPC patients. Together, the results of our analysis that NDUFB8 and ATP5B could be as for local recurrence in analysis of the between NDUFB8 and ATP5B expression with local recurrence-free survival of NPC = = = was for analysis to the of prognostic in a The was for analysis to the of prognostic In this we demonstrate that are to NLRP3 inflammasome activation through mitochondrial OxPhos analysis and iTRAQ we ASC cells and found that they are with OxPhos which mitochondrial and inflammasome We further found that NDUFB8 and ATP5B as markers for local recurrence-free survival in NPC patients. is the to mitochondrial OxPhos inflammasome activation and NPC patients ASC speck which is a for inflammasome activation, can be controlled by various cellular the phosphorylation of ASC A. and regulation of the Mol. Biol. 2017; PubMed Scopus Google Scholar, N. of NLRP3 inflammasome by 2018; PubMed Scopus Google Scholar). We previously that can the to ASC specks upon NLRP3 inflammasome activation, can ASC at and ASC can in speck formation and secretion Chen Chen Ojcius D.M. Chen L.C. the NLRP3 inflammasome by ASC and to PubMed Scopus Google Scholar). have that complex and are for of the inflammasome N. M. Q. J. The complex is for NLRP3 inflammasome PubMed Scopus Google Scholar, C. F. Y. Y. S. Chen W. Q. W. J. Inflammasome by ASC for the PubMed Scopus Google Scholar). However, we the signaling that to and inflammasome speck formation. we the protein expression patterns of ASC and NPC cells, and found that mitochondrial OxPhos proteins are for inflammasome formation and activation in this In we found that the ASC NPC cells were for various mitochondrial with in and mitochondrial protein strongly suggest that there is a between mitochondrial and NLRP3 inflammasome is a in NLRP3 inflammasome activation, as NLRP3 the mitochondrial OxPhos machinery to and A. E. S. S. J. F. D. G. E. J. M. inflammasome activation of Full Text Full Text PDF PubMed Scopus Google Scholar, J. A role for in NLRP3 inflammasome PubMed Scopus Google Scholar). It is known that OxPhos and form a Y. of mitochondrial oxidative phosphorylation and for their PubMed Scopus Google that plays a key role in The of the The PubMed Scopus Google Scholar). OxPhos complex which is a for intracellular also the of OxPhos complex can be by the C. J. A. The mitochondrial an in the 2017; PubMed Scopus Google Scholar). In the study, we observed of OxPhos proteins and in ASC NPC cells, that the two are with inflammasome Our findings are with the that cancer cell with of OxPhos proteins of ROS and to and with cells G. Y. C. F. I. G. S. A. The F. mitochondrial in human Full Text Full Text PDF PubMed Scopus Google Scholar). the of of ROS in cells is to be a key in the NLRP3 inflammasome and the of cancer We previously that high-level NLRP3 inflammasome expression is with better survival in NPC patients (6Chen L.C. Wang L.J. Tsang N.M. Ojcius D.M. Chen C.C. C. Y. Chen C.C. and local recurrence-free survival in nasopharyngeal Mol. PubMed Scopus Google the this was ROS have been to NLRP3 inflammasome activation and the and of cancer Wang M. The role of cellular reactive oxygen species in cancer Cancer Res. 2018; PubMed Scopus Google Scholar). Various cancer (e.g. the ROS to cell death by the E. N. G. a that to mitochondrial and PubMed Scopus Google Scholar). In the study, our analysis of OxPhos complex components that in NPC cells, NDUFB3, and ATP5B production, leading to NLRP3 inflammasome activation and cell pyroptosis. we observed an between expression of NDUFB8 and ATP5B in NPC tumor and this to be with better survival in NPC patients. findings suggest that NDUFB8 and ATP5B in the NLRP3 regulation of NPC treatment. with our expression of ATP5B been with better survival in cancer J. Miao Q. J. G. Chen S. and are markers for the of patients with Mol. PubMed Scopus Google and acute J. S. Y. W. Y. Y. F. M. M. G. of mitochondrial in acute cells and with PubMed Scopus Google Scholar). the findings and our results that and NDUFB8 can be as markers for of local recurrence in NPC patients. In we a previously mitochondrial OxPhos and that NLRP3 inflammasome formation and We further that high-level expression of OxPhos proteins could be as for local recurrence in NPC patients and/or as a therapeutic The for analysis were the the A. N. J. I. G. Y. F. Wang of the and Res. PubMed Scopus Google The of identified proteins are as the with