Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response

Radha Desai; Daniel A. East; Liana Hardy; Danilo Faccenda; Manuel Rigon; James Crosby; María Soledad Alvarez; Aarti Singh; Marta Mainenti; Laura Kuhlman Hussey; Robert Bentham; Gyorgy Szabadkai; Valentina Zappulli; Gurtej K. Dhoot; Lisa E. Romano; Dong Xia; Isabelle Coppens; Anne Hamacher-Brady; J. Paul Chapple; Rosella Abeti; Roland A. Fleck; Gema Vizcay-Barrena; Kenneth Smith; Michelangelo Campanella

doi:10.1126/sciadv.abc9955

Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response

Radha Desai, Daniel A. East, Liana Hardy, Danilo Faccenda, Manuel Rigon, James Crosby, María Soledad Alvarez, Aarti Singh, Marta Mainenti, Laura Kuhlman Hussey, Robert Bentham, Gyorgy Szabadkai, Valentina Zappulli, Gurtej K. Dhoot, Lisa E. Romano, Dong Xia, Isabelle Coppens, Anne Hamacher-Brady, J. Paul Chapple, Rosella AbetiRoland A. Fleck, Gema Vizcay-Barrena, Kenneth Smith, Michelangelo Campanella

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42 Citations (Scopus)

Abstract

Mitochondria drive cellular adaptation to stress by retro-communicating with the nucleus. This process is known as mitochondrial retrograde response (MRR) and is induced by mitochondrial dysfunction. MRR results in the nuclear stabilization of prosurvival transcription factors such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Here, we demonstrate that MRR is facilitated by contact sites between mitochondria and the nucleus. The translocator protein (TSPO) by preventing the mitophagy-mediated segregation o mitochonria is required for this interaction. The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. The latter allows for cholesterol redistribution of cholesterol in the nucleus to sustain the prosurvival response by blocking NF-κB deacetylation. This work proposes a previously unidentified paradigm in MRR: the formation of contact sites between mitochondria and nucleus to aid communication.

Original language	English
Journal	Science Advances
Volume	6
Issue number	51
DOIs	https://doi.org/10.1126/sciadv.abc9955
Publication status	Published - 18 Dec 2020

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Desai, R., East, D. A., Hardy, L., Faccenda, D., Rigon, M., Crosby, J., Alvarez, M. S., Singh, A., Mainenti, M., Hussey, L. K., Bentham, R., Szabadkai, G., Zappulli, V., Dhoot, G. K., Romano, L. E., Xia, D., Coppens, I., Hamacher-Brady, A., Chapple, J. P., ... Campanella, M. (2020). Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response. Science Advances, 6(51). https://doi.org/10.1126/sciadv.abc9955

@article{11746e010ba14911ae5918dc84dbc9de,

title = "Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response",

abstract = "Mitochondria drive cellular adaptation to stress by retro-communicating with the nucleus. This process is known as mitochondrial retrograde response (MRR) and is induced by mitochondrial dysfunction. MRR results in the nuclear stabilization of prosurvival transcription factors such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Here, we demonstrate that MRR is facilitated by contact sites between mitochondria and the nucleus. The translocator protein (TSPO) by preventing the mitophagy-mediated segregation o mitochonria is required for this interaction. The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. The latter allows for cholesterol redistribution of cholesterol in the nucleus to sustain the prosurvival response by blocking NF-κB deacetylation. This work proposes a previously unidentified paradigm in MRR: the formation of contact sites between mitochondria and nucleus to aid communication.",

author = "Radha Desai and East, {Daniel A.} and Liana Hardy and Danilo Faccenda and Manuel Rigon and James Crosby and Alvarez, {Mar{\'i}a Soledad} and Aarti Singh and Marta Mainenti and Hussey, {Laura Kuhlman} and Robert Bentham and Gyorgy Szabadkai and Valentina Zappulli and Dhoot, {Gurtej K.} and Romano, {Lisa E.} and Dong Xia and Isabelle Coppens and Anne Hamacher-Brady and Chapple, {J. Paul} and Rosella Abeti and Fleck, {Roland A.} and Gema Vizcay-Barrena and Kenneth Smith and Michelangelo Campanella",

year = "2020",

month = dec,

day = "18",

doi = "10.1126/sciadv.abc9955",

language = "English",

volume = "6",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

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Desai, R, East, DA, Hardy, L, Faccenda, D, Rigon, M, Crosby, J, Alvarez, MS, Singh, A, Mainenti, M, Hussey, LK, Bentham, R, Szabadkai, G, Zappulli, V, Dhoot, GK, Romano, LE, Xia, D, Coppens, I, Hamacher-Brady, A, Chapple, JP, Abeti, R, Fleck, RA , Vizcay-Barrena, G, Smith, K & Campanella, M 2020, 'Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response', Science Advances, vol. 6, no. 51. https://doi.org/10.1126/sciadv.abc9955

TY - JOUR

T1 - Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response

AU - Desai, Radha

AU - East, Daniel A.

AU - Hardy, Liana

AU - Faccenda, Danilo

AU - Rigon, Manuel

AU - Crosby, James

AU - Alvarez, María Soledad

AU - Singh, Aarti

AU - Mainenti, Marta

AU - Hussey, Laura Kuhlman

AU - Bentham, Robert

AU - Szabadkai, Gyorgy

AU - Zappulli, Valentina

AU - Dhoot, Gurtej K.

AU - Romano, Lisa E.

AU - Xia, Dong

AU - Coppens, Isabelle

AU - Hamacher-Brady, Anne

AU - Chapple, J. Paul

AU - Abeti, Rosella

AU - Fleck, Roland A.

AU - Vizcay-Barrena, Gema

AU - Smith, Kenneth

AU - Campanella, Michelangelo

PY - 2020/12/18

Y1 - 2020/12/18

N2 - Mitochondria drive cellular adaptation to stress by retro-communicating with the nucleus. This process is known as mitochondrial retrograde response (MRR) and is induced by mitochondrial dysfunction. MRR results in the nuclear stabilization of prosurvival transcription factors such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Here, we demonstrate that MRR is facilitated by contact sites between mitochondria and the nucleus. The translocator protein (TSPO) by preventing the mitophagy-mediated segregation o mitochonria is required for this interaction. The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. The latter allows for cholesterol redistribution of cholesterol in the nucleus to sustain the prosurvival response by blocking NF-κB deacetylation. This work proposes a previously unidentified paradigm in MRR: the formation of contact sites between mitochondria and nucleus to aid communication.

AB - Mitochondria drive cellular adaptation to stress by retro-communicating with the nucleus. This process is known as mitochondrial retrograde response (MRR) and is induced by mitochondrial dysfunction. MRR results in the nuclear stabilization of prosurvival transcription factors such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Here, we demonstrate that MRR is facilitated by contact sites between mitochondria and the nucleus. The translocator protein (TSPO) by preventing the mitophagy-mediated segregation o mitochonria is required for this interaction. The complex formed by TSPO with the protein kinase A (PKA), via the A-kinase anchoring protein acyl-CoA binding domain containing 3 (ACBD3), established the tethering. The latter allows for cholesterol redistribution of cholesterol in the nucleus to sustain the prosurvival response by blocking NF-κB deacetylation. This work proposes a previously unidentified paradigm in MRR: the formation of contact sites between mitochondria and nucleus to aid communication.

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U2 - 10.1126/sciadv.abc9955

DO - 10.1126/sciadv.abc9955

M3 - Article

C2 - 33355129

AN - SCOPUS:85098565661

SN - 2375-2548

VL - 6

JO - Science Advances

JF - Science Advances

IS - 51

ER -

Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response

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