Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 32, Pages 16074-16079Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1818830116
Keywords
axon regeneration; mitochondria; ER
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Funding
- Samsung Science and Technology Foundation [SSTF-BA1301003]
- Leading Research Program, National Research Foundation of Korea - Korea government (MEST) [2016R1A3B1905982]
- National Research Foundation of Korea [2016R1A3B1905982] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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