Summary
Despite progress in understanding cellular energy stress responses, the role of metabolic enzymes in these processes remains understudied. Here, we discovered that hexokinase 1 (HK1), a key glycolytic enzyme, clusters into ring-like structures around mitochondria during energy stress. These HK1-rings constrict mitochondria at contact sites with the endoplasmic reticulum (ER) and prevent mitochondrial fission by displacing the dynamin-related protein 1 (Drp1) from mitochondrial constriction sites. Mechanistically, we identified that the lack of ATP and glucose-6-phosphate (G6P) promotes the clustering of HK1. We found several structural features that are critical for the formation of HK1-rings. Our findings highlight that HK1 is a robust energy stress sensor that regulates the shape, position, and connectivity of mitochondria. Thus, the formation of HK1-rings may affect mitochondrial function in energy stress-related pathologies.
Competing Interest Statement
The authors have declared no competing interest.
