Pei Dan-Dan, Sun Jin-Long, Zhu Chun-Hui, Tian Fu-Cong, Jiao Kai, Anderson Matthew R, Yiu Cynthia, Huang Cui, Jin Chang-Xiong, Bergeron Brian E, Chen Ji-Hua, Tay Franklin R, Niu Li-Na
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research Department of Prosthodontics College of Stomatology Xi'an Jiaotong University Xi'an 710004 P. R. China.
State Key Laboratory of Military Stomatology National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Prosthodontics School of Stomatology The Fourth Military Medical University Xi'an 710032 P. R. China.
Adv Sci (Weinh). 2018 Jul 29;5(10):1800873. doi: 10.1002/advs.201800873. eCollection 2018 Oct.
Biomineralization in vertebrates is initiated via amorphous calcium phosphate (ACP) precursors. These precursors infiltrate the extracellular collagen matrix where they undergo phase transformation into intrafibrillar carbonated apatite. Although it is well established that ACP precursors are released from intracellular vesicles through exocytosis, an unsolved enigma in this cell-mediated mineralization process is how ACP precursors, initially produced in the mitochondria, are translocated to the intracellular vesicles. The present study proposes that mitophagy provides the mechanism for transfer of ACP precursors from the dysfunctioned mitochondria to autophagosomes, which, upon fusion with lysosomes, become autolysosomes where the mitochondrial ACP precursors coalesce to form larger intravesicular granules, prior to their release into the extracellular matrix. Apart from endowing the mitochondria with the function of ACP delivery through mitophagy, the present results indicate that mitophagy, triggered upon intramitochondrial ACP accumulation in osteogenic lineage-committed mesenchymal stem cells, participates in the biomineralization process through the BMP/Smad signaling pathway.
脊椎动物中的生物矿化通过无定形磷酸钙（ACP）前体启动。这些前体渗透到细胞外胶原基质中，在那里它们经历相变形成纤维内碳酸化磷灰石。尽管已经明确ACP前体通过胞吐作用从细胞内囊泡释放，但在这个细胞介导的矿化过程中一个尚未解决的谜是，最初在线粒体中产生的ACP前体如何转运到细胞内囊泡。本研究提出，线粒体自噬提供了将ACP前体从功能失调的线粒体转移到自噬体的机制，自噬体与溶酶体融合后成为自溶酶体，线粒体ACP前体在释放到细胞外基质之前在自溶酶体中聚合并形成更大的囊泡内颗粒。除了通过线粒体自噬赋予线粒体ACP传递功能外，本研究结果还表明，在成骨谱系定向间充质干细胞线粒体内ACP积累时触发的线粒体自噬，通过BMP/Smad信号通路参与生物矿化过程。
