Title :
Glucose regulates mitochondrial motility via
Milton modification by
O-GlcNAc transferase
Abstract :
- Cells allocate substantial resources toward monitoring levels of nutrients that can be used for ATP generation by mitochondria
- Among the many specialized cell types, neurons are particularly dependent on mitochondria due to their complex morphology and regional energy needs
- Here, we report a molecular mechanism by which nutrient availability in the form of extracellular glucose and the enzyme O-GlcNAc Transferase ( OGT ), whose activity depends on glucose availability, regulates mitochondrial motility in neurons
- Activation of OGT diminishes mitochondrial motility
- We establish the mitochondrial motor-adaptor protein Milton as a required substrate for OGT to arrest mitochondrial motility by mapping and mutating the key O-GlcNAcylated serine residues serine residues
- We find that the GlcNAcylation state of Milton is altered by extracellular glucose and that OGT alters mitochondrial motility in vivo
- Our findings suggest that, by dynamically regulating Milton GlcNAcylation, OGT tailors mitochondrial dynamics in neurons based on nutrient availability