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These processes rely on the acquisition of distinct cellular properties to enable ligand secretion for cell-cell signaling and initiate morphogenesis through cellular contraction, cell migration, and cell shape change. In this study, we showed that mitochondrial activity and distribution play a key role in bestowing cellular functions on both alveolar epithelial cells and mesenchymal myofibroblasts for generating secondary septa to form alveoli in mice. These results suggest that mitochondrial function is tightly regulated to empower cellular machineries in a spatially specific manner. Indeed, such regulation via mitochondria is required for secretion of ligands, such as platelet-derived growth factor, from alveolar epithelial cells to influence myofibroblast proliferation and contraction\/migration. Moreover, mitochondrial function enables myofibroblast contraction\/migration during alveolar formation. Together, these findings yield novel mechanistic insights into how mitochondria regulate pivotal steps of alveologenesis. They highlight selective utilization of energy in cells and diverse energy demands in different cellular processes during development. Our work serves as a paradigm for studying how mitochondria control tissue patterning.<\/jats:p>","DOI":"10.7554\/elife.68598","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T07:15:22Z","timestamp":1649229322000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.68598","source":"Crossref","is-referenced-by-count":25,"title":["Acquisition of cellular properties during alveolar formation requires differential activity and distribution of mitochondria"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-1328","authenticated-orcid":true,"given":"Kuan","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Cardiovascular Research Institute, University of California","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Yao","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Cardiovascular Research Institute, University of California","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Cardiovascular Research Institute, University of California","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Chuang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Cardiovascular Research Institute, University of California","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Wong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Cardiovascular Research Institute, University of California","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert I","family":"Seed","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, University of California","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L","family":"Nishimura","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, University of California","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Wolters","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-8653","authenticated-orcid":true,"given":"Pao-Tien","family":"Chuang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"Cardiovascular Research Institute, University of California","place":["San Francisco, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"14665","DOI":"10.1073\/pnas.0504750102","article-title":"Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors","volume":"102","author":"Akiyama","year":"2005","journal-title":"PNAS"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105477","article-title":"Characterization of platelet-derived growth factor-A expression in mouse tissues using A lacZ knock-in approach","volume":"9","author":"Andrae","year":"2014","journal-title":"PLOS ONE"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"3551","DOI":"10.1172\/JCI32526","article-title":"Squamous metaplasia amplifies pathologic epithelial-mesenchymal interactions in COPD patients","volume":"117","author":"Araya","year":"2007","journal-title":"The Journal of Clinical Investigation"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2015.76","article-title":"Chronic obstructive pulmonary disease","volume":"1","author":"Barnes","year":"2015","journal-title":"Nature Reviews. 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