Spinal cord injury induces mitochondrial dysfunction and metabolic reprogramming in non-regenerative Xenopus laevis

Spinal cord injury (SCI) causes permanent neurological deficits in mammals. Larval Xenopus laevis regenerate after SCI, but post-metamorphic animals lose this capacity, resembling mammalian response. Because mitochondria and metabolism influence cell survival and tissue repair, we examined mitochondrial dynamics and metabolic responses after SCI in non-regenerative X. laevis. Using imaging, ultrastructural analyses, ATP measurements, and transcriptional profiling, we found that, unlike regenerative stages, non-regenerative spinal cords exhibited a delayed response with mitochondrial altered localization, reduced density, increased area, and structural abnormalities, consistent with dysfunction. Despite these defects, ATP levels increased after injury, coinciding with the upregulation of glycolytic enzymes and markers of lipid catabolism and lipid droplet formation. These findings indicate that SCI in non-regenerative X. laevis triggers metabolic reprogramming toward glycolysis and lipid utilization that may compensate for mitochondrial dysfunction. Our results identify mitochondrial and metabolic responses associated with regenerative failure and provide insight into metabolic states linked to repair.