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

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


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 languageEnglish
JournalScience Advances
Issue number51
Publication statusPublished - 18 Dec 2020


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