Proteomic and metabolomic profiling of acute and chronic stress events associated with military exercises.

By characterizing physiological changes that occur in warfighters during simulated combat, we can start to unravel the key biomolecular components that are linked to physical and cognitive performance. Viable field-based sensors for the warfighter must be rapid and noninvasive. In an effort to facilitate this, we applied a multiomics pipeline to characterize the stress response in the saliva of warfighters to correlate biomolecular changes with overall performance and health. In this study, two different stress models were observed - one of chronic stress and one of acute stress. In both models, significant perturbations in the immune, metabolic, and protein manufacturing/processing systems were observed. However, when differentiating between stress models, specific metabolites associated with the "fight or flight" response and protein folding were seen to be discriminate of the acute stress model.

Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.

Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function.