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COPI Vesicle Disruption Inhibits Mineralization via mTORC1-Mediated Autophagy.

ABSTRACT: Bone mineralization is a sophisticated regulated process composed of crystalline calcium phosphate and collagen fibril. 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.

SUBMITTER: Nie J

PROVIDER: S-EPMC10779376 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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COPI Vesicle Disruption Inhibits Mineralization via mTORC1-Mediated Autophagy.

Nie Jiaming J Ma Shaoyang S Zhang Yuchen Y Yu Shuchen S Yang Jiajia J Li Ang A Pei Dandan D

International journal of molecular sciences 20231226 1

Bone mineralization is a sophisticated regulated process composed of crystalline calcium phosphate and collagen fibril. 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), re ...[more]

PMID: 38203512

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COPI Vesicle Disruption Inhibits Mineralization via mTORC1-Mediated Autophagy.

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COPI Vesicle Disruption Inhibits Mineralization via mTORC1-Mediated Autophagy.

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