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 - Paul Chapple, J.
AU - Abeti, Rosella
AU - Fleck, Roland A.
AU - Vizcay-Barrena, Gema
AU - Smith, Kenneth
AU - Campanella, Michelangelo
N1 - Funding Information:
The research activities lead by M.C. are supported by the following funders, who are gratefully acknowledged: Biotechnology and Biological Sciences Research Council (grant numbers BB/M010384/1 and BB/N007042/1), Rotary Foundation, the Petplan Charitable Trust (Project references: S12-14 and 373-411) and the European Research Council COG 2018-819600_FIRM.
Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved.
PY - 2020/12
Y1 - 2020/12
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-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.
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-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.
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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
M1 - eabc9955
ER -