Year: 2023
Type: article
Abstract: targeting mitochondria to autophagosomes through direct interaction between mito-ATTECs and LC3 on mitochondrial membranes. Subsequently, autophagosomes containing mitochondria rapidly fuse with lysosomes to facilitate the degradation of mitochondria. Therefore, mito-ATTECs circumvent the detrimental effects related to disruption of mitochondrial membrane integrity by inducers routinely used to manipulate mitophagy, and provide a versatile biochemical approach to investigate the physiological roles of mitophagy. Furthermore, we found that sustained mitophagy lead to mitochondrial depletion and autophagic cell death in several malignant cell lines (lethal mitophagy). Among them, apoptosis-resistant malignant melanoma cell lines are particularly sensitive to lethal mitophagy. The therapeutic efficacy of mito-ATTECs has been further evaluated by using subcutaneous and pulmonary metastatic melanoma models. Together, the mitochondrial depletion achieved by mito-ATTECs may demonstrate the general concept of inducing cancer cell lethality through excessive mitochondrial clearance, establishing a promising therapeutic paradigm for apoptosis-resistant tumors.
Source: Chemical Science
DOI: 10.1039/d3sc03600f
Authors: Zhenqi Liu, Geng Qin, Jie Yang, Wenjie Wang, Wenting Zhang, Boxun Lu, Jinsong Ren, Xiaogang Qu
Institutions: University of Science and Technology of China, Chinese Academy of Sciences, Changchun Institute of Applied Chemistry, State Key Laboratory of Rare Earth Resources Utilization, Shanghai Medical College of Fudan University, Fudan University, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Frontiers Center for Brain Science of the Ministry of Education
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4387029271