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However, prior studies utilized lung cancer cells or dissociated animal cells. We sought to better define human nasal epithelial responses to phenazines, including the role of Ca\n                      <jats:sup>2+<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Live cell imaging was used to measure Ca\n                      <jats:sup>2+<\/jats:sup>\n                      and mitochondrial function in RPMI2650 nasal carcinoma cells and primary human nasal epithelial cells (HNECs) cultured in submersion and at air\u2013liquid interface (ALI). Gene expression was measured by quantitative PCR. Ciliary beat frequency (CBF) was quantified by high\u2010speed imaging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pyocyanin, but not 1\u2010HP, increased mitochondrial Ca\n                      <jats:sup>2+<\/jats:sup>\n                      dependent on phospholipase C and endoplasmic reticulum (ER) Ca\n                      <jats:sup>2+<\/jats:sup>\n                      release, correlating with protein kinase C activation. Mitochondrial membrane potential decreased and mitochondrial ROS increased with both pyocyanin and 1\u2010HP in a Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010independent manner. Both pyocyanin and 1\u2010HP decreased viability of RPMI2650s and other squamous carcinoma cell lines over 24\u00a0h, whereas HNECs survived, possibly due to differential regulation of protein homeostasis genes, including activating transcription factor 6 (\n                      <jats:italic>ATF6<\/jats:italic>\n                      ). Mitochondrial ROS was enhanced in CF\u2010CRS ALIs, which may explain why pyocyanin reduced CBF in CF but not non\u2010CF ALIs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signaling is not required for phenazine mitochondrial toxicity. The greater sensitivity of cancer cells to phenazine cytotoxicity necessitates use of primary cells when studying host responses to bacterial phenazines. Enhanced ROS production and ciliotoxicity in CF\u2010CRS may contribute to susceptibility to\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alr.70084","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T13:19:09Z","timestamp":1766150349000},"page":"451-466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of Mitochondrial Toxicity and Cytotoxicity Caused by\n                    <i>Pseudomonas aeruginosa<\/i>\n                    Pyocyanin in Human Nasal Epithelial Cells"],"prefix":"10.1002","volume":"16","author":[{"given":"Joel C.","family":"Thompson","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Division of Rhinology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9487-0782","authenticated-orcid":false,"given":"April","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Division of Rhinology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yobouet Ines","family":"Kouakou","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Division of Rhinology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoey A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Division of Rhinology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil F.","family":"Darwich","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Division of Rhinology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nithin D.","family":"Adappa","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Division of Rhinology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James N.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Division of Rhinology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan M.","family":"Carey","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Division of Rhinology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-6686","authenticated-orcid":false,"given":"Robert J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Division of Rhinology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Physiology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-024-03889-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.02312-22"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00031-19"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2018.11.013"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11051295"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","unstructured":"Z. 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