@article{86e1e48777fe4f9c9d3dfe8f6a233f13,
title = "Lipid storage and lipophagy regulates ferroptosis",
abstract = "The synthesis, storage, and degradation of lipids are highly regulated processes. Impaired lipid metabolism is implicated in inflammation and cell death. Although ferroptosis is a recently described form of regulated cell death driven by lipid peroxidation, the impact of lipid droplets on ferroptosis remains unidentified. Here, we demonstrate that lipophagy, the autophagic degradation of intracellular lipid droplets, promotes RSL3-induced ferroptotic cell death in hepatocytes. Lipid droplet accumulation is increased at the early stage but decreased at the late stage of ferroptosis in mouse or human hepatocytes. Importantly, either genetically enhancing TPD52-dependent lipid storage or blocking ATG5-and RAB7A-dependent lipid degradation prevents RSL3-induced lipid peroxidation and subsequent ferroptosis in vitro and in vivo. These studies support an antioxidant role for lipid droplets in cell death and suggest novel strategies for the inhibition of ferroptosis by targeting the lipophagy pathway.",
keywords = "Autophagy, Ferroptosis, Lipid degradation, Lipid droplets, Lipid storage",
author = "Yuansong Bai and Lingjun Meng and Leng Han and Yuanyuan Jia and Yanan Zhao and Huan Gao and Rui Kang and Xiaofeng Wang and Daolin Tang and Enyong Dai",
note = "Funding Information: We thank Dave Primm (Department of Surgery, University of Texas Southwestern Medical Center) for his critical reading of the manuscript. This work was supported by grants from the US National Institutes of Health (R01CA160417 [D.T.] and R01CA211070 [R.K.]), the American Cancer Society (Research Scholar Grant RSG-16-014-01-CDD [D.T.]), the Natural Science Foundation of Jilin Province of China (20160101062JC [E.D.]), the Health Foundation of the Finance Department of Jilin Province (sczsy201516 [E.D.]), and the National Natural Science Foundation of China (30870355 and 81370497 [E.D.]). Funding Information: We thank Dave Primm (Department of Surgery, University of Texas Southwestern Medical Center) for his critical reading of the manuscript. This work was supported by grants from the US National Institutes of Health ( R01CA160417 [D.T.] and R01CA211070 [R.K.] ), the American Cancer Society (Research Scholar Grant RSG-16-014-01-CDD [D.T.] ), the Natural Science Foundation of Jilin Province of China ( 20160101062JC [E.D.] ), the Health Foundation of the Finance Department of Jilin Province ( sczsy201516 [E.D.] ), and the National Natural Science Foundation of China ( 30870355 and 81370497 [E.D.] ). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2019",
month = jan,
day = "22",
doi = "10.1016/j.bbrc.2018.12.039",
language = "English (US)",
volume = "508",
pages = "997--1003",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",
}