Document Type

Poster

Publication Date

4-30-2020

Institution/Department

Maine Medical Center, Medical Education, Maine Medical Center Research Institute, Center for Molecular Medicine

MeSH Headings

Mitophagy, Osteogenesis, Cell Differentiation, Osteoblasts

Abstract

Osteoblasts generate bone by secreting collagen and mineralizing it in response to various signaling cues. We have previously identified bioenergetic pathways that are active during osteoblastogenesis. We showed that a majority of ATP generated by differentiated osteoblasts is through glycolysis in contrast to undifferentiated cells that are oxidative phosphorylation dependent. To identify mechanisms involved in this shift we hypothesized that increased mitochondrial turnover through mitophagy reprograms metabolism towards glycolysis. Mitophagy is a specialized autophagy process that targets dysfunctional mitochondria to lysosomes for recycling. Utilizing a mitophagy reporter mouse line (MitoQC) we first identified active basal mitophagy in skeletal cells in vivo. In support of our hypothesis we found that differentiating calvarial osteoblasts showed a strong increase in mitophagy. Next, surveying for potential mediators of mitophagy in osteoblasts we identified BNIP3 a protein involved in receptor mediated mitophagy as being upregulated with osteoblast differentiation. Manipulating BNip3 expression, both by knockdown and overexpression showed that BNIP3 positively regulated osteoblast differentiation by targeting mitochondrial metabolism. These sets of data for the first time identify a role for mitochondrial turnover in osteoblast differentiation potentially mediated through BNIP3.

Comments

2020 Costas T. Lambrew Research Retreat

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