Molecular mechanism of glutaminase activation through filamentation and the role of filaments in mitophagy protection.

Glutaminase (GLS), which deaminates glutamine to form glutamate, is a mitochondrial tetrameric protein complex. Although inorganic phosphate (Pi) is known to promote GLS filamentation and activation, the molecular basis of this mechanism is unknown. Here we aimed to determine the molecular mechanism of Pi-induced mouse GLS filamentation and its impact on mitochondrial physiology.

GLS2 is protumorigenic in breast cancers.

Many types of cancers have a well-established dependence on glutamine metabolism to support survival and growth, a process linked to glutaminase 1 (GLS) isoforms. Conversely, GLS2 variants often have tumor-suppressing activity. Triple-negative (TN) breast cancer (testing negative for estrogen, progesterone, and Her2 receptors) has elevated GLS protein levels and reportedly depends on exogenous glutamine and GLS activity for survival.

Glutaminase Affects the Transcriptional Activity of Peroxisome Proliferator-Activated Receptor γ (PPARγ) via Direct Interaction.

Phosphate-activated glutaminases catalyze the deamidation of glutamine to glutamate and play key roles in several physiological and pathological processes. In humans, GLS encodes two multidomain splicing isoforms: KGA and GAC. In both isoforms, the canonical glutaminase domain is flanked by an N-terminal region that is folded into an EF-hand-like four-helix bundle.