Immunity 48, 542–55 (2018)
Mitochondria–endoplasmic reticulum (ER) interactions are known to modulate mitochondrial respiration in non-immune cells. In Immunity, Bantug et al. show that mitochondria–ER junctions in effector memory (EM) CD8+ T cells represent a signaling hub in which mTORC2–AKT–GSK3β signaling induces the oxidation of glucose to drive rapid production of the cytokine IFN-γ. More mitochondria–ER contacts are found in EM CD8+ T cells than in naive CD8+ T cells. Inhibition of GSK3β by mTORC2–AKT at these junctions allows recruitment of the kinase HK-I to the ion channel VDAC on the outer membrane of the mitochondria and the influx of substrates important for mitochondrial respiration. Destabilization of mitochondria–ER contracts or inhibition of the HK-1–VDAC interaction interferes with the rapid production of IFN-γ in activated EM CD8+ T cells through inhibition of glycolysis and, possibly, of glycolysis-dependent histone acetylation at the Ifng promoter.
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Visan, I. Mitochondria–ER hubs. Nat Immunol 19, 510 (2018). https://doi.org/10.1038/s41590-018-0097-z
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DOI: https://doi.org/10.1038/s41590-018-0097-z