Evidence of complete myofibril remodeling after severe damage in adult Drosophila.

Muscle function hinges on the resilience of myofibrils to mechanical harm, yet the mechanisms of adult muscle recovery after severe injury have remained elusive. Researchers have devised a Drosophila model that induces and tracks extensive myofibril damage and subsequent recovery in adult femur muscles. Intense muscle depolarization triggers widespread disruption of myofibrils, often resulting in the near-total obliteration of Z-disc structures.

Surprisingly, myofibril structure and muscle function rebound to a large extent within days, indicating a considerable ability for myofibril reconstruction in adult femur muscles. The team categorized myofibril damage into two primary states: mild and severe, with mild damage preceding severe damage as muscles age, implying a gradual deterioration and repair failure of myofibrils.

Filamins, proteins involved in mechanosignaling, were found to play a pivotal role in efficient myofibril remodeling. In response to damage, wild-type filamins shift away from the Z-disc and gather outside the myofibrils, while constitutively open filamins stay attached to the Z-disc and, conversely, closed filamins redistribute but exacerbate damage and hinder recovery.

These results imply that effective repair necessitates dynamic shifts between filamin conformations, and that filamin redistribution is an active part of the damage response rather than merely a byproduct of muscle injury. As muscles age, filamins progressively detach from the Z-disc, leading to a rise in muscle damage, with severe damage emerging after the onset of mild damage.

Overall, these findings unveil a previously unrecognized capacity of adult muscle to reassemble damaged myofibrils and pinpoint filamin mechanosignaling as a critical element of this repair process. The study offers a framework for understanding how impaired mechanosensing might contribute to age-related muscle deterioration and muscle disorders.