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Vacuolar\u2010type H<jats:sup>+<\/jats:sup>\u2010translocating ATPases and a pyrophosphatase are thought to enable vacuoles to accumulate protons against their electrochemical potential. However, recent studies pointed to the ATPase located at the trans\u2010Golgi network\/early endosome (TGN\/EE) to contribute to vacuolar acidification in a manner not understood as of now. Here, we combined experimental data and computational modeling to test different hypotheses for vacuolar acidification mechanisms. For this, we analyzed different models with respect to their ability to describe existing experimental data. To better differentiate between alternative acidification mechanisms, new experimental data have been generated. By fitting the models to the experimental data, we were able to prioritize the hypothesis in which vesicular trafficking of Ca<jats:sup>2+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>\u2010antiporters from the TGN\/EE to the vacuolar membrane and the activity of ATP\u2010dependent Ca<jats:sup>2+<\/jats:sup>\u2010pumps at the tonoplast might explain the residual acidification observed in Arabidopsis mutants defective in vacuolar proton pump activity. The presented modeling approach provides an integrative perspective on vacuolar pH regulation in Arabidopsis and holds potential to guide further experimental work.<\/jats:p>","DOI":"10.1111\/tpj.15251","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T15:50:37Z","timestamp":1617033037000},"page":"1541-1556","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["An integrative view on vacuolar pH homeostasis in <i>Arabidopsis thaliana<\/i>: Combining mathematical modeling and experimentation"],"prefix":"10.1111","volume":"106","author":[{"given":"Pascal","family":"Holzheu","sequence":"first","affiliation":[{"name":"Department of Modeling of Biological Processes COS Heidelberg\/Bioquant Heidelberg University Im Neuenheimer Feld 267 Heidelberg 69120 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