| Literature DB >> 31110288 |
Amado Carreras-Sureda1,2,3, Fabián Jaña2,4, Hery Urra1,2,3, Sylvere Durand5,6, David E Mortenson7, Alfredo Sagredo1,2,3, Galdo Bustos2,4,8, Younis Hazari1,2,3, Eva Ramos-Fernández9, Maria L Sassano10, Philippe Pihán1,2,3, Alexander R van Vliet10, Matías González-Quiroz1,2,3, Angie K Torres11, Cheril Tapia-Rojas11, Martijn Kerkhofs12, Rubén Vicente13, Randal J Kaufman14, Nibaldo C Inestrosa9, Christian Gonzalez-Billault2,15,16, R Luke Wiseman7, Patrizia Agostinis10, Geert Bultynck14, Felipe A Court2,8, Guido Kroemer5,6,17,18,19, J César Cárdenas2,4,8,20, Claudio Hetz21,22,23,24,25.
Abstract
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 IRE1α as a structural determinant of MAMs that controls mitochondrial calcium uptake. IRE1α deficiency resulted in marked alterations in mitochondrial physiology and energy metabolism under resting conditions. IRE1α 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 IRE1α at MAMs from its canonical role in the unfolded protein response. These observations were validated in vivo in the liver of IRE1α conditional knockout mice, revealing broad implications for cellular metabolism. Our results support an alternative function of IRE1α in orchestrating the communication between the endoplasmic reticulum and mitochondria to sustain bioenergetics.Entities:
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Year: 2019 PMID： 31110288 PMCID： PMC7246037 DOI： 10.1038/s41556-019-0329-y
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.824