{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:22:30Z","timestamp":1790443350858,"version":"4.1.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>The main objective of this study is to define the mechanisms by which mitochondria control vascular smooth muscle cell (VSMC) migration and impact neointimal hyperplasia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              The multifunctional CaMKII (Ca\n              <jats:sup>2+<\/jats:sup>\n              \/calmodulin-dependent kinase II) in the mitochondrial matrix of VSMC drove a feed-forward circuit with the mitochondrial Ca\n              <jats:sup>2+<\/jats:sup>\n              uniporter (MCU) to promote matrix Ca\n              <jats:sup>2+<\/jats:sup>\n              influx. MCU was necessary for the activation of mitochondrial CaMKII (mtCaMKII), whereas mtCaMKII phosphorylated MCU at the regulatory site S92 that promotes Ca\n              <jats:sup>2+<\/jats:sup>\n              entry. mtCaMKII was necessary and sufficient for platelet-derived growth factor\u2013induced mitochondrial Ca\n              <jats:sup>2+<\/jats:sup>\n              uptake. This effect was dependent on MCU. mtCaMKII and MCU inhibition abrogated VSMC migration and mitochondrial translocation to the leading edge. Overexpression of wild-type MCU, but not MCU S92A, mutant in MCU\n              <jats:sup>\u2212<\/jats:sup>\n              <jats:sup>\/\u2212<\/jats:sup>\n              VSMC rescued migration and mitochondrial mobility. Inhibition of microtubule, but not of actin assembly, blocked mitochondrial mobility. The outer mitochondrial membrane GTPase Miro-1 promotes mitochondrial mobility via microtubule transport but arrests it in subcellular domains of high Ca\n              <jats:sup>2+<\/jats:sup>\n              concentrations. In Miro-1\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              VSMC, mitochondrial mobility and VSMC migration were abolished, and overexpression of mtCaMKII or a CaMKII inhibitory peptide in mitochondria (mtCaMKIIN) had no effect. Consistently, inhibition of mtCaMKII increased and prolonged cytosolic Ca\n              <jats:sup>2+<\/jats:sup>\n              transients. mtCaMKII inhibition diminished phosphorylation of focal adhesion kinase and myosin light chain, leading to reduced focal adhesion turnover and cytoskeletal remodeling. In a transgenic model of selective mitochondrial CaMKII inhibition in VSMC, neointimal hyperplasia was significantly reduced after vascular injury.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              These findings identify mitochondrial CaMKII as a key regulator of mitochondrial Ca\n              <jats:sup>2+<\/jats:sup>\n              uptake via MCU, thereby controlling mitochondrial translocation and VSMC migration after vascular injury.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.310951","type":"journal-article","created":{"date-parts":[[2018,3,29]],"date-time":"2018-03-29T09:05:19Z","timestamp":1522314319000},"page":"1333-1345","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":75,"title":["CaMKII (Ca\n            <sup>2+<\/sup>\n            \/Calmodulin-Dependent Kinase II) in Mitochondria of Smooth Muscle Cells Controls Mitochondrial Mobility, Migration, and Neointima Formation"],"prefix":"10.1161","volume":"38","author":[{"given":"Emily K.","family":"Nguyen","sequence":"first","affiliation":[{"name":"From the Department of Internal Medicine, Carver College of Medicine (E.K.N., O.M.K., P.N., K.B., W.H.T., I.M.G.)"},{"name":"Interdisciplinary Program in Molecular and Cellular Biology (E.K.N.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olha M.","family":"Koval","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Carver College of Medicine (E.K.N., O.M.K., P.N., K.B., W.H.T., I.M.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Noble","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Carver College of Medicine (E.K.N., O.M.K., P.N., K.B., W.H.T., I.M.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Broadhurst","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Carver College of Medicine (E.K.N., O.M.K., P.N., K.B., W.H.T., I.M.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Allamargot","sequence":"additional","affiliation":[{"name":"Central Microscopy Research Facility, Carver College of Medicine (C.A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Medicinal and Natural Products Chemistry, Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy (M.W.)"},{"name":"High Throughput Screening Facility (M.W.)"},{"name":"Department of Biochemistry, Carver College of Medicine (M.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Strack","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Carver College of Medicine (S.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Thiel","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Carver College of Medicine (E.K.N., O.M.K., P.N., K.B., W.H.T., I.M.G.)"},{"name":"Fran\u00e7ois Abboud Cardiovascular Research Center (W.H.T., I.M.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella M.","family":"Grumbach","sequence":"additional","affiliation":[{"name":"From the Department of Internal Medicine, Carver College of Medicine (E.K.N., O.M.K., P.N., K.B., W.H.T., I.M.G.)"},{"name":"Fran\u00e7ois Abboud Cardiovascular Research Center (W.H.T., I.M.G.)"},{"name":"Iowa City Veterans Affairs Healthcare System (I.M.G.), University of Iowa, Iowa 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