Safe lysosomal sequestration of ferrous iron is mediated via cholesterol shielding and drives senescence and ferroptosis resistance.

Izumi Yanatori, Tasuku Hirayama, Raku Son, Yasuhiro Murakawa, Yuta Matsuoka, Yuki Sugiura, Masato Niwa, Tatsuya Katsuno, Masahiko Tsujimoto, Hiroyuki Yasui, Atsuyasu Sato, Makoto Nakanishi, Kazuhiro Iwai

Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. [email protected] of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. [email protected]. · pubmed

Paper

Abstract

Iron accumulation is a conserved hallmark of cellular as well as organismal aging, yet its mechanistic role in senescence remains largely elusive. Here we show that the accumulation of ferrous iron (Fe

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Research summary

The paper demonstrates that lysosomal sequestration of ferrous iron, mediated by cholesterol shielding, drives cellular senescence while conferring resistance to ferroptosis. This work is highly relevant because it identifies a specific mechanistic link between a conserved hallmark of aging (iron accumulation) and the cellular state of senescence, offering a potential target for interventions aimed at delaying the functional decline associated with aging rather than merely treating downstream symptoms.

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