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Desai R, East DA, Hardy L, et al. Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response. Sci Adv. 2020;6(51)doi: 10.1126/sciadv.abc9955.
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., Abeti, R., Fleck, R. A., Vizcay-Barrena, G., Smith, K., & 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
Desai, Radha, et al. "Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response." Science advances vol. 6,51 (2020). doi: https://doi.org/10.1126/sciadv.abc9955
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. Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response. Sci Adv. 2020 Dec 18;6(51). doi: 10.1126/sciadv.abc9955. Print 2020 Dec. PMID: 33355129.
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Sci Adv. 2020 Dec 18;6(51). doi: 10.1126/sciadv.abc9955. Print 2020 Dec.

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

Science advances

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

Affiliations

  1. Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK.
  2. Department of Cell and Developmental Biology, Consortium for Mitochondrial Research (CfMR), University College London, Gower Street, London WC1E 6BT, UK.
  3. Department of Biomedical Science, University of Padua, Via Ugo Bassi, 35131 Padua, Italy.
  4. Francis Crick Institute, Midland Road, London NW1 AT, UK.
  5. Department of Comparative Biomedicine and Food Sciences, University of Padua, Viale dell'Universita' 16, 35020 Legnaro (PD), Italy.
  6. William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London EC1M 6BQ, UK.
  7. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Baltimore, Baltimore, MD 21205, USA.
  8. Ataxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
  9. Centre for Ultrastructural Imaging, King's College London, London SE1 1UL, UK.
  10. Pathobiology and Population Sciences, The Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire AL9 7TA, UK.
  11. Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, Royal College Street, London NW1 0TU, UK. [email protected].

PMID: 33355129 DOI: 10.1126/sciadv.abc9955

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.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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