Work

Spastin regulates autophagy via interaction with ATG5 in spinal cord injury

Year: 2026

Type: article

Abstract: Spinal cord injury represents a devastating central nervous system trauma frequently leading to permanent neurological deficits. Autophagy, a cellular process for clearing damaged organelles and protein aggregates, is crucial for maintaining intracellular homeostasis. Modulation of autophagy can positively influence the repair and functional recovery of injured neurons. Our data demonstrates that inhibition of spastin disrupts autophagic flux, resulting in the accumulation of autophagosomes. Mechanistically, we found that spastin interacts with ATG5 to facilitate autophagosome formation. Interference with spastin, either through inhibition or knockdown, attenuates this interaction, subsequently impairing the assembly of the ATG12-5-16L1 complex and hindering autophagy initiation. Consequently, intracellular macromolecular debris accumulates, lysosomal function is compromised, and spinal cord injury repair is exacerbated. Collectively, these findings establish a role for the spastin-ATG5 interaction in autophagosome biogenesis and demonstrate that spastin inhibition effectively blocks autophagic flux.

Source: Cellular and Molecular Life Sciences

DOI: 10.1007/s00018-026-06414-8