A research group led by Professor Yoshiyuki Horio of the Department of Pharmacology, Sapporo Medical University School of Medicine has revealed that the longevity gene SIRT1 (sirtuin) works to close the torn hole in the cell membrane.
SIRT1 is a member of Sir2 that works to extend the lifespan of yeast, and is known to improve muscular dystrophy when activated.However, it has not been clarified why SIRT1 improves muscular dystrophy.
In this study, we created a knockout mouse that lost SIRT1 in skeletal muscle, and this mouse showed symptoms similar to muscular dystrophy, had weaker muscle strength and less exercise endurance than normal mice, and was forced to exercise. It turned out that the muscles would be broken if they were made to do so.From this, it was found that SIRT1 is necessary for maintaining the muscle strength and endurance of skeletal muscle, and that the muscle becomes fragile when SIRT1 disappears.
It was also found that SIRT1 exists directly under the cell membrane in skeletal muscle, so we suspected that SIRT1 might be involved in cell membrane repair.Therefore, we made a hole in the cell membrane of muscle cells using laser light and observed the repair process of the cell membrane of living cells in detail with a video.As a result, in normal cells, vesicles (vesicles) accumulate directly under the hole, and the membrane is quickly repaired by covering the hole with a dome-shaped structure, but when SIRT1 is disabled, the vegekul does not collect. , Membrane repair did not occur.
This study shows for the first time that SIRT1 is required to repair holes in cell membranes.Since it is known that muscular dystrophy is fragile, it is possible that the cell membrane repair mechanism is involved in the mechanism that activation of SIRT1 improves muscular dystrophy.
So far, it has been known that genetic defects in proteins involved in membrane repair cause muscular dystrophy, but little is known about its regulatory mechanism.In the future, we will investigate the involvement of SIRT1 in membrane repair in detail and aim to elucidate the mechanism of membrane repair.
Paper information:[PLOS ONE] SIRT1 deficiency interferes with membrane resealing after cell membrane injury