PT  - JOURNAL ARTICLE
AU  - Keiko Kono
AU  - Yoshikazu Johmura
AU  - Yohsuke Moriyama
AU  - Yumiko Masukagami
AU  - Koutarou Nishimura
AU  - Hunter Barbee
AU  - Hiroshi Takase
AU  - Shinju Sugiyama
AU  - Yoshikatsu Sato
AU  - Tetsuya Higashiyama
AU  - Makoto Nakanishi
TI  - Plasma membrane damage limits replicative lifespan in yeast and human fibroblasts
AID  - 10.1101/2021.03.26.437120
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.26.437120
4099  - http://biorxiv.org/content/early/2021/03/27/2021.03.26.437120.short
4100  - http://biorxiv.org/content/early/2021/03/27/2021.03.26.437120.full
AB  - Plasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. Here, using yeast and human fibroblasts, we show that cellular senescence, irreversible cell cycle arrest contributing to organismal aging, is the third outcome of PMD. To identify the genes essential for PMD response, we performed a systematic yeast genome-wide screen. The screen identified 48 genes. The top hits in the screen are the endosomal sorting complexes required for transport (ESCRT) genes. Strikingly, the replicative lifespan regulator genes are enriched in our 48 hits, and indeed, PMD limits the replicative lifespan in budding yeast; the ESCRT activator AAA-ATPase VPS4-overexpression extends it. In normal human fibroblasts, PMD induces cellular senescence via p53. Our study demonstrates that PMD limits replicative lifespan in two different eukaryotic cell types and highlights an underappreciated but ubiquitous senescent cell subtype, namely PMD-dependent senescent cells.Competing Interest StatementThe authors have declared no competing interest.