Journal
FRONTIERS IN CELLULAR NEUROSCIENCE
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2019.00316
Keywords
mitochondria; transfer; astrocytes; neuronal cells; GFAP mutation; Alexander disease
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Funding
- National Key Research and Development Program of China [2018YFA0108000, 2018YFA0108003]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010309]
- National Key Research and Development Program of China Stem Cell and Translational Research [2016YFA0101200, 2016YFA0101202]
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Mitochondria are the critical organelles for energy metabolism and cell survival in eukaryotic cells. Recent studies demonstrated that mitochondria can intercellularly transfer between mammalian cells. In neural cells, astrocytes transfer mitochondria into neurons in a CD38-dependent manner. Here, using co-culture system of neural cell lines, primary neural cells, and human pluripotent stem cell (hPSC)-derived neural cells, we further revealed that mitochondria dynamically transferred between astrocytes and also from neuronal cells into astrocytes, to which CD38/cyclic ADP-ribose signaling and mitochondrial Rho GTPases (MIRO1 and MIRO2) contributed. The transfer consequently elevated mitochondrial membrane potential in the recipient cells. By introducing Alexander disease (AxD)-associated hotspot mutations (R79C, R239C) into GFAP gene of hPSCs and subsequently inducing astrocyte differentiation, we found that GFAP mutations impaired mitochondrial transfer from astrocytes and reduced astrocytic CD38 expression. Thus, our study suggested that mitochondria dynamically transferred between neural cells and revealed that AxD-associated mutations in GFAP gene disrupted the astrocytic transfer, providing a potential pathogenic mechanism in AxD.
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