GATOR2 complex protein MIOS

MIOS (GATOR2 complex protein MIOS) is a component of the GATOR2 signaling complex that functions as an activator of the mTORC1 amino acid-sensing pathway (UniProt: Q9NXC5). Within GATOR2, MIOS prevents autoubiquitination of WDR24, the catalytic subunit; the complex indirectly activates mTORC1 by inhibiting the GATOR1 subcomplex through ubiquitin-mediated degradation of GATOR1 components when amino acids are abundant. The GATOR2 complex is also required for brain myelination (UniProt: Q9NXC5).

mTORC1 signaling is integral to neuronal metabolism and synaptic plasticity, with the GATOR2–GATOR1 axis serving as a critical metabolic checkpoint in the brain. Dysregulation of this pathway has been implicated in neurological disease contexts (UniProt: Q9NXC5).

MIOS is elevated in Alzheimer's disease brain tissue: human post-mortem AD brain shows increased MIOS expression compared to age-matched controls (mean log2FC +0.34, Chaparral AD proteomics). This upregulation may reflect compensatory mTORC1 activation or altered amino acid sensing in the AD brain proteome, though the functional consequence of elevated MIOS in AD pathology remains to be determined.