STING1 Promotes Ferroptosis Through MFN1/2-Dependent Mitochondrial Fusion

• DOI: 10.3389/fcell.2021.698679
• Publication Date: 2021-06-14T09:18:24Z
• Authors: Changfeng Li; Jiao Liu; Wen Hou; Rui Kang; Daolin Tang
• Keywords: MFN1; PINK1; MFN2

Ferroptosis is a type of iron-dependent regulated cell death caused by the disruption that occurs when oxidative stress and antioxidant defenses interact, then driven lipid peroxidation subsequent plasma membrane ruptures. The regulation ferroptosis involves many factors, including crosstalk between subcellular organelles, such as mitochondria, endoplasmic reticulum (ER), lysosomes, droplets, peroxisomes. Here, we show ER protein STING1 (also known STING or TMEM173) promotes in human pancreatic cancer lines increasing MFN1/2-dependent mitochondrial fusion, but not mitophagy-mediated removal. classic inducer erastin, sulfasalazine, induces accumulation where it binds to MFN1/2 trigger leading reactive oxygen species production peroxidation. Consequently, vitro xenograft mouse models genetic depletion (but mitophagy regulator PINK1 PRKN) reduces sensitivity cells ferroptosis. These findings only establish new fusion-dependent mechanism, also indicate potential strategy for enhancing ferroptosis-based therapy.