Priority Research Paper Volume 10, Issue 8 pp 1856—1866
GRSF1 suppresses cell senescence
- 1 Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
received: March 31, 2018 ; accepted: August 2, 2018 ; published: August 7, 2018 ;https://doi.org/10.18632/aging.101516
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Copyright: Noh et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
A prominent phenotype triggered by the loss of mitochondrial homeostasis is cellular senescence, characterized by cessation of growth and a senescence-associated secretory phenotype (SASP). We identified the G-rich RNA sequence-binding factor 1 (GRSF1) as a major mitochondrial protein implicated in this response. GRSF1 levels declined in senescent cells through reduced protein stability, and lowering GRSF1 abundance caused mitochondrial stress leading to elevated production of superoxide, increased DNA damage foci, and diminished cell proliferation. In addition, reducing GRSF1 increased the activity of a senescence-associated β-galactosidase (SA-β-gal) and the production and secretion of the SASP factor interleukin 6 (IL6). Together, our findings indicate that the decline in GRSF1 levels during cellular senescence contributes to impairing mitochondrial function, elevating ROS and DNA damage, suppressing growth, and implementing a pro-inflammatory program.