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

Dan dan Pei, Jin long Sun, Chun hui Zhu, Fucong Tian, Kai Jiao, Matthew R. Anderson, Cynthia Yiu, Cui Huang, Chang xiong Jin, Brian Edward Bergeron, Ji hua Chen, Franklin Chi Meng Tay, Li na Niu

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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.

Original languageEnglish (US)
Article number1800873
JournalAdvanced Science
Volume5
Issue number10
DOIs
StatePublished - Oct 2018

Keywords

  • amorphous calcium phosphate
  • mineralization
  • mitophagy
  • osteogenesis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Chemical Engineering
  • General Materials Science
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • General Engineering
  • General Physics and Astronomy

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