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2016 ; 12
(8
): 1425-8
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Autophagy promotes ferroptosis by degradation of ferritin
#MMPMID27245739
Hou W
; Xie Y
; Song X
; Sun X
; Lotze MT
; Zeh HJ 3rd
; Kang R
; Tang D
Autophagy
2016[Aug]; 12
(8
): 1425-8
PMID27245739
show ga
Macroautophagy/autophagy is an evolutionarily conserved degradation pathway that
maintains homeostasis. Ferroptosis, a novel form of regulated cell death, is
characterized by a production of reactive oxygen species from accumulated iron
and lipid peroxidation. However, the relationship between autophagy and
ferroptosis at the genetic level remains unclear. Here, we demonstrated that
autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts
and cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7
limited erastin-induced ferroptosis with decreased intracellular ferrous iron
levels, and lipid peroxidation. Remarkably, NCOA4 (nuclear receptor coactivator
4) was a selective cargo receptor for the selective autophagic turnover of
ferritin (namely ferritinophagy) in ferroptosis. Consistently, genetic inhibition
of NCOA4 inhibited ferritin degradation and suppressed ferroptosis. In contrast,
overexpression of NCOA4 increased ferritin degradation and promoted ferroptosis.
These findings provide novel insight into the interplay between autophagy and
regulated cell death.
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