期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：32
页码：16074-16079
DOI：10.1073/pnas.1818830116
出版社：The National Academy of Sciences of the United States of America
摘要：Translocation of the endoplasmic reticulum (ER) and mitochondria to the site of axon injury has been shown to facilitate axonal regeneration; however, the existence and physiological importance of ER–mitochondria tethering in the injured axons are unknown. Here, we show that a protein linking ER to mitochondria, the glucose regulated protein 75 (Grp75), is locally translated at axon injury site following axotomy, and that overexpression of Grp75 in primary neurons increases ER–mitochondria tethering to promote regrowth of injured axons. We find that increased ER–mitochondria tethering elevates mitochondrial Ca2+ and enhances ATP generation, thereby promoting regrowth of injured axons. Furthermore, intrathecal delivery of lentiviral vector encoding Grp75 to an animal with sciatic nerve crush injury enhances axonal regeneration and functional recovery. Together, our findings suggest that increased ER–mitochondria tethering at axonal injury sites may provide a therapeutic strategy for axon regeneration.
