Citations 1
Mitochondrial RNA cytosolic leakage drives the SASP
Victorelli, Stella , Eppard, Madeline, Woo, Seung‐Hwa , Everts, Stacia , Martini, Hélène , Pirius, Nicholas, Franco, Ana Catarina , Han, Yeaeun , Saul, Dominik , Splinter, Patrick L., O’Hara, Steven P. , Valenzuela-Pérez, Lucía , Lee, Hyun Se Kim , Jurk, Diana , Everts, Stacia P A, LaRusso, Nicholas F , Hirsova, Petra , Passos, João F , Jurk, Diana , Kim Lee, Hyun Se , Saul, Dominik , Lee, Gung , Han, Nuan , Liang, Eugene Y., Nóvoa, Eva , Nogueiras, Rubén , Morgenthaler, Olivia , LaRusso, Nicholas F. , Passos, João F.
No container title available | August 26, 2024 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Senescent cells secrete proinflammatory factors known as the senescence-associated secretory phenotype (SASP), contributing to tissue dysfunction and aging. Mitochondrial dysfunction is a key feature of senescence, influencing SASP via mitochondrial DNA (mtDNA) release and cGAS/STING pathway activation. Here, we demonstrate that mitochondrial RNA (mtRNA) also accumulates in the cytosol of senescent cells, activating RNA sensors RIG-I and MDA5, leading to MAVS aggregation and SASP induction. Inhibition of these RNA sensors significantly reduces SASP factors. Furthermore, BAX and BAK plays a key role in mtRNA leakage during senescence, and their deletion diminishes SASP expression in vitro and in a mouse model of Metabolic Dysfunction Associated Steatohepatitis (MASH). These findings highlight mtRNA's role in SASP regulation and its potential as a therapeutic target for mitigating age-related inflammation.