Lei, Xue
Mayo Clinic
Sanford Burnham Prebys Medical Discovery Institute
Citations 1
Mitochondrial metabolism and epigenetic crosstalk drive the SASP
Martini, Hélène , Birch, Jodie , Victorelli, Stella , Lagnado, Anthony B. , Pirius, Nicholas, Han, Yeaeun , Havas, Aaron , Jurk, Diana , Adams, Peter D. , Passos, João F. , Victorelli, Stella , Lagnado, Anthony , Franco, Ana, Lee, Gung, Han, Yeaeun , Rowsey, Jennifer, Gaspar-Maia, Alexandre , Havas, Aaron , Porritt, Rebecca , Maddocks, Oliver , Jurk, Diana , Khosla, Sundeep , Adams, Peter , Passos, João F , Marques, Francisco Madeira , Franco, Ana Catarina , Lee, Gung , Rowsey, Jennifer L. , Ismail, Wazim Mohammed , Mazzone, Amelia , Espe, Tianna, Hitosugi, Taro , Li, Ya , Washington, Alexander M. , Murad, Rabi , Lei, Xue , Espíndola‐Netto, Jair Machado , Saul, Dominik , Khosla, Sundeep , Kostallari, Enis , Gaspar‐Maia, Alexandre
No container title available | December 5, 2024 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Senescent cells drive tissue dysfunction through the senescence-associated secretory phenotype (SASP). We uncovered a central role for mitochondria in the epigenetic regulation of the SASP, where mitochondrial-derived metabolites, specifically citrate and acetyl-CoA, fuel histone acetylation at SASP gene loci, promoting their expression. We identified the mitochondrial citrate carrier (SLC25A1) and ATP-citrate lyase (ACLY) as critical for this process. Inhibiting these pathways selectively suppresses SASP without affecting cell cycle arrest, highlighting their potential as therapeutic targets for age-related inflammation. Notably, SLC25A1 inhibition reduces systemic inflammation and extends healthspan in aged mice, establishing mitochondrial metabolism as pivotal to the epigenetic control of aging.