Plasma membrane mediated GLUT10 mitochondrial targeting regulates intracellular ascorbic acid homeostasis

Jose, A. C.; Syu, Y.-W.; Lai, H.-W.; Tsai, M.-Y.; Jiang, Y.-F.; Hsu, S.-C.; Lin, P.-Y.; Huang, W.-C.; Chu, W.-C.; Fu, C.-Y.; Lee, Y.-C.

doi:10.1101/2025.01.09.632083

bioRxiv · 10.1101/2025.01.09.632083

Plasma membrane mediated GLUT10 mitochondrial targeting regulates intracellular ascorbic acid homeostasis

Jose, A. C.·Syu, Y.-W.·Lai, H.-W.·Tsai, M.-Y.·Jiang, Y.-F.·Hsu, S.-C.·Lin, P.-Y.·Huang, W.-C.·Chu, W.-C.·Fu, C.-Y.·Lee, Y.-C.

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Abstract

Regulation of intracellular ascorbic acid (AA) levels is critical for connective tissue development and maintenance, but the underlying mechanisms remain unclear. In this study, we uncover a novel regulatory role of glucose transporter 10 (GLUT10) in AA homeostasis through a noncanonical trafficking pathway from the endomembrane system to mitochondria, traditionally considered as separate entities. We demonstrate that GLUT10 transit from ER to mitochondria through the plasma membrane (PM) and endosomes increases under stress conditions. This PM localization enhances the transport of dehydroascorbic acid (DHA), the oxidized form of AA, thereby maintaining intracellular AA levels. Disruption of this trafficking impairs AA homeostasis. Our findings reveal a previously unrecognized localization of GLUT10 at the PM and endosomes, highlighting a novel communication between endomembrane system and mitochondria for proetin redistribution, which is essential for maintaining intracellular AA homeostasis and facilitating environmental adaptation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=144 SRC="FIGDIR/small/632083v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@17ac1d1org.highwire.dtl.DTLVardef@4aa2f3org.highwire.dtl.DTLVardef@101849org.highwire.dtl.DTLVardef@aa9c26_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Jose, A. C., Syu, Y.-W., Lai, H.-W., Tsai, M.-Y., Jiang, Y.-F., Hsu, S.-C., Lin, P.-Y., Huang, W.-C., Chu, W.-C., Fu, C.-Y., Lee, Y.-C.. 2025-01-13. Plasma membrane mediated GLUT10 mitochondrial targeting regulates intracellular ascorbic acid homeostasis. https://doi.org/10.1101/2025.01.09.632083

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