%0 Journal Article
%T Non-canonical function of IRE1¦Á determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics
%J -
%D 2019
%R https://doi.org/10.1038/s41556-019-0329-y
%X Mitochondria-associated membranes (MAMs) are central microdomains that fine-tune bioenergetics by the local transfer of calcium from the endoplasmic reticulum to the mitochondrial matrix. Here, we report an unexpected function of the endoplasmic reticulum stress transducer IRE1¦Á as a structural determinant of MAMs that controls mitochondrial calcium uptake. IRE1¦Á deficiency resulted in marked alterations in mitochondrial physiology and energy metabolism under resting conditions. IRE1¦Á determined the distribution of inositol-1,4,5-trisphosphate receptors at MAMs by operating as a scaffold. Using mutagenesis analysis, we separated the housekeeping activity of IRE1¦Á at MAMs from its canonical role in the unfolded protein response. These observations were validated in vivo in the liver of IRE1¦Á conditional knockout mice, revealing broad implications for cellular metabolism. Our results support an alternative function of IRE1¦Á in orchestrating the communication between the endoplasmic reticulum and mitochondria to sustain bioenergetics
%U https://www.nature.com/articles/s41556-019-0329-y