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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. 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.

SUBMITTER: Pekkurnaz G

PROVIDER: S-EPMC4224014 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Glucose regulates mitochondrial motility via Milton modification by O-GlcNAc transferase.

Pekkurnaz Gulcin G Trinidad Jonathan C JC Wang Xinnan X Kong Dong D Schwarz Thomas L TL

Cell 20140701 1

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 mo ...[more]

PMID: 24995978

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Glucose regulates mitochondrial motility via Milton modification by O-GlcNAc transferase.

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Glucose regulates mitochondrial motility via Milton modification by O-GlcNAc transferase.

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