期刊
AUTOPHAGY
卷 15, 期 1, 页码 172-173出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2018.1526611
关键词
Cancer; CD274; HMGB1; immunometabolism; iron; PINK1; PRKN; SLC25A28; SLC25A37
类别
资金
- US National Institutes of Health [R01GM115366, R01CA160417, R01CA211070, R01GM127791, R01GM053396]
- Natural Science Foundation of Guangdong Province [2016A030308011]
- American Cancer Society [RSG-16-014-01-CDD]
- National Natural Science Foundation of China [31671435, 81400132, 81772508]
- Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2017)
- National Institutes of Health [R01GM115366, R01CA160417, R01CA211070, R01GM127791, R01GM053396]
Mitochondrial quality control is an essential process required to maintain cellular homeostasis and functions. Mutations of PINK1 and PRKN/PARK2 contribute to the risk of Parkinson disease. Our recent findings indicate that depletion of Pink1 and Prkn promotes pancreatic tumorigenesis in KRAS-driven engineered mouse models. Mechanistically, PINK1- and PRKN-mediated autophagic degradation of mitochondrial iron importers (e.g., SLC25A37 and SLC25A28) suppresses pancreatic tumor growth by attenuating mitochondrial iron accumulation, inflammasome activation, HMGB1 release, and subsequent immune checkpoint expression. Consequently, pharmacological or genetic inhibition of mitochondrial iron-dependent signals prolongs animal survival and reverses pancreatic tumor phenotype in vivo. Thus, PINK1- and PRKN-mediated immunometabolism provides new insights into the tumor microenvironment and could be a suitable target for new pancreatic cancer treatments.
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