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Adv Sci (Weinh). 2018 Jul 29;5(10):1800873. doi: 10.1002/advs.201800873. eCollection 2018 Oct.

Contribution of Mitophagy to Cell-Mediated Mineralization: Revisiting a 50-Year-Old Conundrum.

Author information

1
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.
2
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.
3
Department of Endodontics The Dental College of Georgia Augusta University Augusta GA 30912 USA.
4
Paediatric Dentistry Unit of the Faculty of Dentistry Prince Philip Dental Hospital University of Hong Kong Hong Kong SAR 999077 P. R. China.
5
Department of Prosthodontics School and Hospital of Stomatology Wuhan University Wuhan 430079 P. R. China.

Abstract

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.

KEYWORDS:

amorphous calcium phosphate; mineralization; mitophagy; osteogenesis

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