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Although voltage\u2010dependent Na\n                    <jats:sup>+<\/jats:sup>\n                    channels are abundantly expressed in \u03b2 cells and activated by glucose, their role in communicating with mitochondria is unresolved. Here, we combined fluorescent Na\n                    <jats:sup>+<\/jats:sup>\n                    , Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , and ATP imaging, electrophysiological analysis with tetrodotoxin (TTX)\u2010dependent block of the Na\n                    <jats:sup>+<\/jats:sup>\n                    channel, and molecular manipulation of mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transporters to study the communication between Na\n                    <jats:sup>+<\/jats:sup>\n                    channels and mitochondria. We show that TTX inhibits glucose\u2010dependent depolarization and blocks cytosolic Na\n                    <jats:sup>+<\/jats:sup>\n                    and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    responses and their propagation into mitochondria. TTX\u2010sensitive mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx was largely blocked by knockdown of the mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    uniporter (MCU) expression. Knockdown of the mitochondrial Na\n                    <jats:sup>+<\/jats:sup>\n                    \/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    exchanger (NCLX) and Na\n                    <jats:sup>+<\/jats:sup>\n                    dose response analysis demonstrated that NCLX mediates the mitochondrial Na\n                    <jats:sup>+<\/jats:sup>\n                    influx and is tuned to sense the TTX\u2010sensitive cytosolic Na\n                    <jats:sup>+<\/jats:sup>\n                    responses. Finally, TTX blocked glucose\u2010dependent mitochondrial Ca\n                    <jats:sup>2+<\/jats:sup>\n                    rise, mitochondrial metabolic activity, and ATP production. Our results show that communication of the Na\n                    <jats:sup>+<\/jats:sup>\n                    channels with mitochondria shape both global Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and metabolism signals linked to insulin secretion in \u03b2 cells.\u2014Nita, I. I., Hershfinkel, M., Kantor, C., Rutter, G. A., Lewis, E. C., Sekler, I. Pancreatic \u03b2\u2010cell Na\n                    <jats:sup>+<\/jats:sup>\n                    channels control global Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling and oxidative metabolism by inducing Na\n                    <jats:sup>+<\/jats:sup>\n                    and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    responses that are propagated into mitochondria.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    28, 3301\u20133312 (2014).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.13-248161","type":"journal-article","created":{"date-parts":[[2014,4,9]],"date-time":"2014-04-09T23:31:24Z","timestamp":1397086284000},"page":"3301-3312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Pancreatic \u03b2\u2010cell Na\n                    <sup>+<\/sup>\n                    channels control global Ca\n                    <sup>2+<\/sup>\n                    signaling and oxidative metabolism by inducing Na\n                    <sup>+<\/sup>\n                    and Ca\n                    <sup>2+<\/sup>\n                    responses that are propagated into mitochondria"],"prefix":"10.1096","volume":"28","author":[{"given":"Iulia I.","family":"Nita","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Hershfinkel","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chase","family":"Kantor","sequence":"additional","affiliation":[{"name":"Section of Cell Biology, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy A.","family":"Rutter","sequence":"additional","affiliation":[{"name":"Section of Cell Biology, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli C.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Health Sciences Ben\u2010Gurion University of the Negev Beer\u2010Sheva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Sekler","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology Ben\u2010Gurion University of the Negev Beer\u2010Sheva 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