Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics.

Autor: Carreras-Sureda A; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile., Jaña F; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile., Urra H; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile., Durand S; Equipe Labellisée par la Ligue contre le cancer, Université Paris Descartes, Université Sorbonne Paris Cité, Université Paris Diderot, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.; Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France., Mortenson DE; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA., Sagredo A; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile., Bustos G; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile., Hazari Y; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile., Ramos-Fernández E; Center for Aging and Regeneration, Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontifical Catholic University of Chile, Santiago, Chile., Sassano ML; Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, VIB-KU Leuven Center for Cancer Biology, KU Leuven, Leuven, Belgium., Pihán P; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile., van Vliet AR; Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, VIB-KU Leuven Center for Cancer Biology, KU Leuven, Leuven, Belgium., González-Quiroz M; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile., Torres AK; Laboratory of Neurobiology of Aging, Centro de Biología Celular y Biomedicina, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile., Tapia-Rojas C; Laboratory of Neurobiology of Aging, Centro de Biología Celular y Biomedicina, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile., Kerkhofs M; Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine and Leuven Kanker Instituut, KU Leuven, Leuven, Belgium., Vicente R; Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain., Kaufman RJ; Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA., Inestrosa NC; Center for Aging and Regeneration, Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontifical Catholic University of Chile, Santiago, Chile., Gonzalez-Billault C; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Buck Institute for Research on Aging, Novato, CA, USA.; Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile., Wiseman RL; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA., Agostinis P; Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, VIB-KU Leuven Center for Cancer Biology, KU Leuven, Leuven, Belgium., Bultynck G; Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA., Court FA; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile., Kroemer G; Equipe Labellisée par la Ligue contre le cancer, Université Paris Descartes, Université Sorbonne Paris Cité, Université Paris Diderot, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.; Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France.; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.; Suzhou Institute for Systems Biology, Chinese Academy of Sciences, Suzhou, China., Cárdenas JC; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile.; Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.; Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA., Hetz C; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile. chetz@hsph.harvard.edu.; FONDAP Geroscience Center for Brain Health and Metabolism, Santiago, Chile. chetz@hsph.harvard.edu.; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile. chetz@hsph.harvard.edu.; Buck Institute for Research on Aging, Novato, CA, USA. chetz@hsph.harvard.edu.; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA. chetz@hsph.harvard.edu.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2019 Jun; Vol. 21 (6), pp. 755-767. Date of Electronic Publication: 2019 May 20.
DOI: 10.1038/s41556-019-0329-y
Abstrakt: 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.
Databáze: MEDLINE
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