IRE1α的非典型功能决定了线粒体相关的内质网组成，以控制钙的转运和生物能。,Nature Cell Biology

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IRE1α的非典型功能决定了线粒体相关的内质网组成，以控制钙的转运和生物能。
Nature Cell Biology ( IF 17.3 ) Pub Date : 2019-05-20 , DOI: 10.1038/s41556-019-0329-y
Amado Carreras-Sureda _{1,

2,

3} , Fabián Jaña _{2,

4} , Hery Urra _{1,

2,

3} , Sylvere Durand _{5,

6} , David E Mortenson ₇ , Alfredo Sagredo _{1,

2,

3} , Galdo Bustos _{2,

4,

8} , Younis Hazari _{1,

2,

3} , Eva Ramos-Fernández ₉ , Maria L Sassano ₁₀ , Philippe Pihán _{1,

2,

3} , Alexander R van Vliet ₁₀ , Matías González-Quiroz _{1,

2,

3} , Angie K Torres ₁₁ , Cheril Tapia-Rojas ₁₁ , Martijn Kerkhofs ₁₂ , Rubén Vicente ₁₃ , Randal J Kaufman ₁₄ , Nibaldo C Inestrosa ₉ , Christian Gonzalez-Billault _{2,

15,

16} , R Luke Wiseman ₇ , Patrizia Agostinis ₁₀ , Geert Bultynck ₁₄ , Felipe A Court _{2,

8} , Guido Kroemer _{5,

6,

17,

18,

19} , J César Cárdenas _{2,

4,

8,

20} , Claudio Hetz _{1,

2,

3,

15,

21}

Affiliation

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.
Anatomy and Developmental Biology Program, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
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.
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Santiago, Chile.
Center for Aging and Regeneration, Department of Cell and Molecular Biology, Faculty of Biological Sciences, Pontifical Catholic University of Chile, Santiago, Chile.
Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, VIB-KU Leuven Center for Cancer Biology, KU Leuven, Leuven, Belgium.
Laboratory of Neurobiology of Aging, Centro de Biología Celular y Biomedicina, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile.
Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine and Leuven Kanker Instituut, KU Leuven, Leuven, Belgium.
Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Buck Institute for Research on Aging, Novato, CA, USA.
Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.
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.
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA.
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.

线粒体相关膜（MAMs）是中央微区，可通过钙从内质网向线粒体基质的局部转移来微调生物能。在这里，我们报告内质网应激传感器IRE1α作为控制线粒体钙摄取的MAM的结构决定因素的意外功能。IRE1α缺乏导致静止状态下线粒体生理和能量代谢发生明显变化。IRE1α通过充当支架来确定MAM处肌醇-1,4,5-三磷酸酯受体的分布。使用诱变分析，我们将IRE1α在MAM的管家活性与其在未折叠蛋白应答中的典型作用分开。这些观察结果在IRE1α条件性基因敲除小鼠的肝脏中得到了验证，揭示了对细胞代谢的广泛影响。我们的结果支持IRE1α在协调内质网和线粒体之间的通讯以维持生物能方面的替代功能。

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更新日期：2019-05-21

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