RESUMO
Metabolic enzymes can adapt during energy stress, but the consequences of these adaptations remain understudied. Here, we discovered that hexokinase 1 (HK1), a key glycolytic enzyme, forms rings around mitochondria during energy stress. These HK1-rings constrict mitochondria at contact sites with the endoplasmic reticulum (ER) and mitochondrial dynamics protein (MiD51). HK1-rings prevent mitochondrial fission by displacing the dynamin-related protein 1 (Drp1) from mitochondrial fission factor (Mff) and mitochondrial fission 1 protein (Fis1). The disassembly of HK1-rings during energy restoration correlated with mitochondrial fission. Mechanistically, we identified that the lack of ATP and glucose-6-phosphate (G6P) promotes the formation of HK1-rings. Mutations that affect the formation of HK1-rings showed that HK1-rings rewire cellular metabolism toward increased TCA cycle activity. Our findings highlight that HK1 is an energy stress sensor that regulates the shape, connectivity, and metabolic activity of mitochondria. Thus, the formation of HK1-rings may affect mitochondrial function in energy-stress-related pathologies.
RESUMO
BACKGROUND: Capillary hemangiomas of spinal nerve root, mostly affecting the cauda equina, are extremely rare. CASE PRESENTATION: A 20-year old man was presented with back pain, radiculopathy, and urogenital symptoms. Magnetic resonance images revealed an intradural extramedullary mass, isointense in T1-weighted and hyperintense in T2-weighted images, with noticeable post injection enhancement. The clinical and radiological findings simulated neurinoma.However, a pinkish lesion was removed surgically and histopathological examination revealed lobules of capillary vessels separated by fibrous tissue, suggesting capillary hemangioma. CONCLUSION: Although rare and sometimes indistinguishable from more common lesion, capillary hemangioma should be in differential diagnosis of any enhancing intradural extramedullary mass at the level of cauda equina or conus medullaris.
