2. Academic Validation
  3. Identification of hyperoxidized PRDX3 as a ferroptosis marker reveals ferroptotic damage in chronic liver diseases

Identification of hyperoxidized PRDX3 as a ferroptosis marker reveals ferroptotic damage in chronic liver diseases

  • Mol Cell. 2023 Nov 2;83(21):3931-3939.e5. doi: 10.1016/j.molcel.2023.09.025.
Shaojie Cui 1,  Anchal Ghai 2,  Yaqin Deng 3,  Shili Li 3,  Ruihui Zhang 4,  Christopher Egbulefu 2,  Guosheng Liang 5,  Samuel Achilefu 2,  Jin Ye 6
Affiliations

Affiliations

  • 1 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: shaojie.cui@utsouthwestern.edu.
  • 2 Department of Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 3 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 4 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 5 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA; Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 6 Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: jin.ye@utsouthwestern.edu.
PMID: 37863053 DOI: 10.1016/j.molcel.2023.09.025
Abstract

Ferroptosis, a regulated cell death pathway driven by accumulation of phospholipid peroxides, has been challenging to identify in physiological conditions owing to the lack of a specific marker. Here, we identify hyperoxidized peroxiredoxin 3 (PRDX3) as a marker for Ferroptosis both in vitro and in vivo. During Ferroptosis, mitochondrial lipid peroxides trigger PRDX3 hyperoxidation, a posttranslational modification that converts a Cys thiol to sulfinic or sulfonic acid. Once hyperoxidized, PRDX3 translocates from mitochondria to plasma membranes, where it inhibits cystine uptake, thereby causing Ferroptosis. Applying hyperoxidized PRDX3 as a marker, we determined that Ferroptosis is responsible for death of hepatocytes in mouse models of both alcoholic and nonalcoholic fatty liver diseases, the most prevalent chronic liver disorders. Our study highlights the importance of Ferroptosis in pathophysiological conditions and opens the possibility to treat these liver diseases with drugs that inhibit Ferroptosis.

Keywords

AFLD; NAFLD; PRDX3; cell death marker; ferroptosis; hyperoxidation.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z