粒体自噬
程序性细胞死亡
线粒体
细胞生物学
癌细胞
癌症研究
细胞凋亡
生物
胰腺癌
线粒体ROS
活性氧
化学
癌症
自噬
生物化学
遗传学
作者
Gilles Rademaker,Yasmine Boumahd,Raphaël Peiffer,Sandy Anania,Tom Wissocq,Maude Liégeois,Géraldine Luis,Nor Eddine Sounni,Ferman Agirman,Naïma Maloujahmoum,Pascal De Tullio,Marc Thiry,Akeila Bellahcène,Vincent Castronovo,Olivier Peulen
出处
期刊:Redox biology
[Elsevier]
日期:2022-07-01
卷期号:53: 102324-102324
被引量:25
标识
DOI:10.1016/j.redox.2022.102324
摘要
Myoferlin, an emerging oncoprotein, has been associated with a low survival in several cancer types including pancreas ductal adenocarcinoma where it controls mitochondria structure and respiratory functions. Owing to the high susceptibility of KRAS-mutated cancer cells to iron-dependent cell death, ferroptosis, and to the high iron content in mitochondria, we investigated the relation existing between mitochondrial integrity and iron-dependent cell death. We discovered that myoferlin targeting with WJ460 pharmacological compound triggered mitophagy and ROS accumulation culminating with lipid peroxidation and apoptosis-independent cell death. WJ460 caused a reduction of the abundance of ferroptosis core regulators xc- cystine/glutamate transporter and GPX-4. Mitophagy inhibitor Mdivi1 and iron chelators inhibited the myoferlin-related ROS production and restored cell growth. Additionally, we reported a synergic effect between ferroptosis inducers, erastin and RSL3, and WJ460.
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