ADAPTING TO STARVATION: ENZYMES QUINARY STRUCTURES SHAPES THE CELL

The quinary structure of enzymes, representing the most intricate level of protein organization, underscores the dynamic interactions of enzymes within the cellular milieu. These interactions, which include self-association and non-covalent bonding with various cellular components, profoundly influence enzyme functionality, stability, and regulatory mechanisms. Our research posits that under nutrient-deprived conditions, several human enzymes can engage in quinary structuring through self-association. We employed techniques such as fluorescence optical microscopy, Cryo-Electron Microscopy, and Cryo-Electron Tomography to demonstrate how glutaminase forms long helical filaments within the mitochondria of glutamine-starved cells. This structuring not only influences mitochondrial morphology but also determines the mitochondrial fate. Similarly, Cystathionine beta-synthase (CBS), a crucial enzyme for producing glutathione, cysteine, and hydrogen sulfide, forms higher-order oligomers in methionine-deprived conditions. These observations suggest that enzymes can self-organize within cells in response to nutrient availability, playing a critical role in cellular adaptation and restructuring. Our findings are beginning to reveal how enzyme self-organization is a vital aspect of cellular response to environmental stresses.

This work was supported by FAPESP (# 2021/05726-6) and CNPEM