CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers

CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1’s molecular functions, regulatory me...

Full description

Saved in:
Bibliographic Details
Main Authors: Jiasen Sun, Hui Ren, Jiawen Wang, Xiang Xiao, Lin Zhu, Yanyan Wang, Lili Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-10-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2024.1458716/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850200892650815488
author Jiasen Sun
Hui Ren
Jiawen Wang
Xiang Xiao
Lin Zhu
Yanyan Wang
Lili Yang
author_facet Jiasen Sun
Hui Ren
Jiawen Wang
Xiang Xiao
Lin Zhu
Yanyan Wang
Lili Yang
author_sort Jiasen Sun
collection DOAJ
description CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1’s molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotransferase, CHAC1 degrades glutathione, affecting calcium signaling and mitochondrial function. Its regulation involves transcription factors like ATF4 and ATF3, which control CHAC1 mRNA expression. CHAC1 is crucial for maintaining redox balance and regulating cell death pathways in cancer. Its elevated levels are associated with poor prognosis in many cancers, indicating its potential as a biomarker and therapeutic target. Additionally, CHAC1 influences non-cancerous diseases such as neurodegenerative and cardiovascular disorders. Therapeutically, targeting CHAC1 could increase cancer cell sensitivity to ferroptosis, aiding in overcoming resistance to standard treatments. This review compiles current knowledge and recent discoveries, emphasizing CHAC1’s vital role in human diseases and its potential in diagnostic and therapeutic applications.
format Article
id doaj-art-95372f6df46749cfa18a2044e1c3bfad
institution OA Journals
issn 2296-634X
language English
publishDate 2024-10-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Cell and Developmental Biology
spelling doaj-art-95372f6df46749cfa18a2044e1c3bfad2025-08-20T02:12:10ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-10-011210.3389/fcell.2024.14587161458716CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancersJiasen Sun0Hui Ren1Jiawen Wang2Xiang Xiao3Lin Zhu4Yanyan Wang5Lili Yang6Department of Gastroenterology, Ankang Central Hospital, Ankang, Shaanxi, ChinaDepartment of Cardiovascular Disease, Ankang Central Hospital, Ankang, Shaanxi, ChinaDepartment of Cardiovascular Disease, Ankang Central Hospital, Ankang, Shaanxi, ChinaDepartment of Gastroenterology, Ankang Central Hospital, Ankang, Shaanxi, ChinaDepartment of Cardiovascular Disease, Ankang Central Hospital, Ankang, Shaanxi, ChinaDepartment of Cardiovascular Disease, Ankang Central Hospital, Ankang, Shaanxi, ChinaDepartment of Cardiovascular Disease, Ankang Central Hospital, Ankang, Shaanxi, ChinaCHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1’s molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotransferase, CHAC1 degrades glutathione, affecting calcium signaling and mitochondrial function. Its regulation involves transcription factors like ATF4 and ATF3, which control CHAC1 mRNA expression. CHAC1 is crucial for maintaining redox balance and regulating cell death pathways in cancer. Its elevated levels are associated with poor prognosis in many cancers, indicating its potential as a biomarker and therapeutic target. Additionally, CHAC1 influences non-cancerous diseases such as neurodegenerative and cardiovascular disorders. Therapeutically, targeting CHAC1 could increase cancer cell sensitivity to ferroptosis, aiding in overcoming resistance to standard treatments. This review compiles current knowledge and recent discoveries, emphasizing CHAC1’s vital role in human diseases and its potential in diagnostic and therapeutic applications.https://www.frontiersin.org/articles/10.3389/fcell.2024.1458716/fullferroptosiscell deathunfold protein responseendoplasmic reticulum stresscancerglutathione
spellingShingle Jiasen Sun
Hui Ren
Jiawen Wang
Xiang Xiao
Lin Zhu
Yanyan Wang
Lili Yang
CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers
Frontiers in Cell and Developmental Biology
ferroptosis
cell death
unfold protein response
endoplasmic reticulum stress
cancer
glutathione
title CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers
title_full CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers
title_fullStr CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers
title_full_unstemmed CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers
title_short CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers
title_sort chac1 a master regulator of oxidative stress and ferroptosis in human diseases and cancers
topic ferroptosis
cell death
unfold protein response
endoplasmic reticulum stress
cancer
glutathione
url https://www.frontiersin.org/articles/10.3389/fcell.2024.1458716/full
work_keys_str_mv AT jiasensun chac1amasterregulatorofoxidativestressandferroptosisinhumandiseasesandcancers
AT huiren chac1amasterregulatorofoxidativestressandferroptosisinhumandiseasesandcancers
AT jiawenwang chac1amasterregulatorofoxidativestressandferroptosisinhumandiseasesandcancers
AT xiangxiao chac1amasterregulatorofoxidativestressandferroptosisinhumandiseasesandcancers
AT linzhu chac1amasterregulatorofoxidativestressandferroptosisinhumandiseasesandcancers
AT yanyanwang chac1amasterregulatorofoxidativestressandferroptosisinhumandiseasesandcancers
AT liliyang chac1amasterregulatorofoxidativestressandferroptosisinhumandiseasesandcancers