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

Amado Carreras-Sureda; Fabián Jaña; Hery Urra; Sylvere Durand; David E. Mortenson; Alfredo Sagredo; Galdo Bustos; Younis Hazari; Eva Ramos-Fernández; Maria L. Sassano; Philippe Pihán; Alexander R. van Vliet; Matías González-Quiroz; Angie K. Torres; Cheril Tapia-Rojas; Martijn Kerkhofs; Rubén Vicente; Randal J. Kaufman; Nibaldo C. Inestrosa; Christian Gonzalez-Billault; R. Luke Wiseman; Patrizia Agostinis; Geert Bultynck; Felipe A. Court; Guido Kroemer; J. César Cárdenas; Claudio Hetz

doi:10.1038/s41556-019-0329-y

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

Amado Carreras-Sureda, Fabián Jaña, Hery Urra, Sylvere Durand, David E. Mortenson, Alfredo Sagredo, Galdo Bustos, Younis Hazari, Eva Ramos-Fernández, Maria L. Sassano, Philippe Pihán, Alexander R. van Vliet, Matías González-Quiroz, Angie K. Torres, Cheril Tapia-Rojas, Martijn Kerkhofs, Rubén Vicente, Randal J. Kaufman, Nibaldo C. Inestrosa, Christian Gonzalez-BillaultR. Luke Wiseman, Patrizia Agostinis, Geert Bultynck, Felipe A. Court, Guido Kroemer, J. César Cárdenas, Claudio Hetz

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

178 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Pages (de - à)	755-767
Nombre de pages	13
journal	Nature Cell Biology
Volume	21
Numéro de publication	6
Les DOIs	https://doi.org/10.1038/s41556-019-0329-y
état	Publié - 1 juin 2019

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10.1038/s41556-019-0329-y

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Carreras-Sureda, A., Jaña, F., Urra, H., Durand, S., Mortenson, D. E., Sagredo, A., Bustos, G., Hazari, Y., Ramos-Fernández, E., Sassano, M. L., Pihán, P., van Vliet, A. R., González-Quiroz, M., Torres, A. K., Tapia-Rojas, C., Kerkhofs, M., Vicente, R., Kaufman, R. J., Inestrosa, N. C., ... Hetz, C. (2019). Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics. Nature Cell Biology, 21(6), 755-767. https://doi.org/10.1038/s41556-019-0329-y

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title = "Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics",

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.",

author = "Amado Carreras-Sureda and Fabi{\'a}n Ja{\~n}a and Hery Urra and Sylvere Durand and Mortenson, {David E.} and Alfredo Sagredo and Galdo Bustos and Younis Hazari and Eva Ramos-Fern{\'a}ndez and Sassano, {Maria L.} and Philippe Pih{\'a}n and {van Vliet}, {Alexander R.} and Mat{\'i}as Gonz{\'a}lez-Quiroz and Torres, {Angie K.} and Cheril Tapia-Rojas and Martijn Kerkhofs and Rub{\'e}n Vicente and Kaufman, {Randal J.} and Inestrosa, {Nibaldo C.} and Christian Gonzalez-Billault and Wiseman, {R. Luke} and Patrizia Agostinis and Geert Bultynck and Court, {Felipe A.} and Guido Kroemer and C{\'a}rdenas, {J. C{\'e}sar} and Claudio Hetz",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2019",

month = jun,

day = "1",

doi = "10.1038/s41556-019-0329-y",

language = "English",

volume = "21",

pages = "755--767",

journal = "Nature Cell Biology",

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Carreras-Sureda, A, Jaña, F, Urra, H, Durand, S, Mortenson, DE, Sagredo, A, Bustos, G, Hazari, Y, Ramos-Fernández, E, Sassano, ML, Pihán, P, van Vliet, AR, González-Quiroz, M, Torres, AK, Tapia-Rojas, C, Kerkhofs, M, Vicente, R, Kaufman, RJ, Inestrosa, NC, Gonzalez-Billault, C, Wiseman, RL, Agostinis, P, Bultynck, G, Court, FA, Kroemer, G, Cárdenas, JC & Hetz, C 2019, 'Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics', Nature Cell Biology, VOL. 21, Numéro 6, p. 755-767. https://doi.org/10.1038/s41556-019-0329-y

TY - JOUR

T1 - Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics

AU - Carreras-Sureda, Amado

AU - Jaña, Fabián

AU - Urra, Hery

AU - Durand, Sylvere

AU - Mortenson, David E.

AU - Sagredo, Alfredo

AU - Bustos, Galdo

AU - Hazari, Younis

AU - Ramos-Fernández, Eva

AU - Sassano, Maria L.

AU - Pihán, Philippe

AU - van Vliet, Alexander R.

AU - González-Quiroz, Matías

AU - Torres, Angie K.

AU - Tapia-Rojas, Cheril

AU - Kerkhofs, Martijn

AU - Vicente, Rubén

AU - Kaufman, Randal J.

AU - Inestrosa, Nibaldo C.

AU - Gonzalez-Billault, Christian

AU - Wiseman, R. Luke

AU - Agostinis, Patrizia

AU - Bultynck, Geert

AU - Court, Felipe A.

AU - Kroemer, Guido

AU - Cárdenas, J. César

AU - Hetz, Claudio

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

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U2 - 10.1038/s41556-019-0329-y

DO - 10.1038/s41556-019-0329-y

M3 - Article

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SN - 1465-7392

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EP - 767

JO - Nature Cell Biology

JF - Nature Cell Biology

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