期刊
CELL RESEARCH
卷 28, 期 8, 页码 833-854出版社
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/s41422-018-0065-z
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资金
- National Natural Science Foundation of China (NSFC) [31671392, 31471280]
- National Key Research and Development Program of China, Stem Cell and Translational Research [2016YFA0100501]
- Intramural Research Program of the National Institute of Neurological Disorders and Stroke, US National Institutes of Health
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [ZIANS002992] Funding Source: NIH RePORTER
The endoplasmic reticulum (ER) is composed of the nuclear envelope, perinuclear sheets and a peripheral tubular network. The peripheral ER and mitochondria form tight contacts at specific subdomains, which coordinate the functions of the two organelles and are required for multiple cellular processes such as Ca2+ transfer and apoptosis. However, it is largely unknown how ER morphology and ER-mitochondria signaling are dynamically regulated under different physiological or pathological conditions such as DNA damage. Here we show that the peripheral, tubular ER undergoes significant extension in response to DNA damage, and that this process is dependent on p53-mediated transcriptional activation of the ER-shaping proteins REEP1, REEP2 and EI24 (alias PIG8). This promotes the formation of ER-mitochondria contacts through EI24 and the mitochondrial outer membrane protein VDAC2, facilitates Ca2+ transfer from ER to mitochondria and promotes DNA damage-induced apoptosis. Thus, we identify a unique DNA damage response pathway involving alterations in ER morphology, ER-mitochondria signaling, and apoptosis.
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