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Autophagy, an evolutionarily conserved degradation system, whereby double-membrane vesicles deliver intracellular macromolecules and organelles to lysosomes for degradation, has recently been shown to play an essential role in mineralization. However, the formation of autophagosomes in mineralization remains to be determined. Here, we show that Coat Protein Complex I (COPI), responsible for Golgi-to-ER transport, plays a pivotal role in autophagosome formation in mineralization. COPI vesicles were increased after osteoinduction, and COPI vesicle disruption impaired osteogenesis. Mechanistically, COPI regulates autophagy activity via the mTOR complex 1 (mTORC1) pathway, a key regulator of autophagy. Inhibition of mTOR1 rescues the impaired osteogenesis by activating autophagy. Collectively, our study highlights the functional importance of COPI in mineralization and identifies COPI as a potential therapeutic target for treating bone-related diseases.<\/jats:p>","DOI":"10.3390\/ijms25010339","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T04:40:44Z","timestamp":1703565644000},"page":"339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["COPI Vesicle Disruption Inhibits Mineralization via mTORC1-Mediated Autophagy"],"prefix":"10.3390","volume":"25","author":[{"given":"Jiaming","family":"Nie","sequence":"first","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyang","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuchen","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Pei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi\u2019an Jiaotong University, Xi\u2019an 710004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a031229","DOI":"10.1101\/cshperspect.a031229","article-title":"Mechanism of Bone Mineralization","volume":"8","author":"Murshed","year":"2018","journal-title":"Cold Spring Harb. 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