Mitochondria form contact sites with the nucleus to couple pro-survival retrograde response
Year: 2020
Type: article
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-кB). 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-кB deacetylation. This work proposes a previously unidentified paradigm in MRR: the formation of contact sites between mitochondria and nucleus to aid communication.
Authors: 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
Institutions: University of London, Royal Veterinary College, University College London, University of Padua, The Francis Crick Institute, Queen Mary University of London, William Harvey Research Institute, Johns Hopkins University, UCL Queen Square Institute of Neurology, King's College London, Centre for Ultrastructural Imaging
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: Petplan Charitable Trust
OpenAlex ID: W3102104890