Bacterial Homologs of Progestin and AdipoQ Receptors (PAQRs) Affect Membrane Energetics Homeostasis but Not Fluidity.

Membrane potential homeostasis is essential for cell survival. Defects in membrane potential lead to pleiotropic phenotypes, consistent with the central role of membrane energetics in cell physiology. Homologs of the progestin and AdipoQ receptors (PAQRs) are conserved in multiple phyla of Bacteria and Eukarya. In eukaryotes, PAQRs are proposed to modulate membrane fluidity and fatty acid (FA) metabolism. The role of bacterial homologs has not been elucidated. Here, we use Escherichia coli and Bacillus subtilis to show that bacterial PAQR homologs, which we name "TrhA," have a role in membrane energetics homeostasis. Using transcriptional fusions, we show that E. coli TrhA (encoded by yqfA) is part of the unsaturated fatty acid biosynthesis regulon. Fatty acid analyses and physiological assays show that a lack of TrhA in both E. coli and B. subtilis (encoded by yplQ) provokes subtle but consistent changes in membrane fatty acid profiles that do not translate to control of membrane fluidity. Instead, membrane proteomics in E. coli suggested a disrupted energy metabolism and dysregulated membrane energetics in the mutant, though it grew similarly to its parent. These changes translated into a disturbed membrane potential in the mutant relative to its parent under various growth conditions. Similar dysregulation of membrane energetics was observed in a different E. coli strain and in the distantly related B. subtilis. Together, our findings are consistent with a role for TrhA in membrane energetics homeostasis, through a mechanism that remains to be elucidated. IMPORTANCE Eukaryotic homologs of the progestin and AdipoQ receptor family (PAQR) have been shown to regulate membrane fluidity by affecting, through unknown mechanisms, unsaturated fatty acid (FA) metabolism. The bacterial homologs studied here mediate small and consistent changes in unsaturated FA metabolism that do not seem to impact membrane fluidity but, rather, alter membrane energetics homeostasis. Together, the findings here suggest that bacterial and eukaryotic PAQRs share functions in maintaining membrane homeostasis (fluidity in eukaryotes and energetics for bacteria with TrhA homologs).

The association of depression with platelet activation: evidence for a treatment effect.

BACKGROUND: Depression is associated with an increased risk of cardiovascular disease (CVD). Although the mechanism is uncertain, prothrombotic and inflammatory factors may play a role. OBJECTIVES: As platelets play a key role in CVD, we determined first, whether depressed individuals had more activated platelets than non-depressed individuals and second, whether treatment of depression reduced platelet activation levels. PATIENTS/METHODS: We recruited 108 depressed outpatients and 45 control subjects all without a history of CVD. After psychological assessment, the depressed patients were offered treatment with medication and/or psychotherapy. Flow cytometric markers of platelet activation and level of depression were assessed at baseline and at 4 weeks and 6 months after treatment. RESULTS: Depression was associated with increased platelet activation with a higher number of circulating CD62p (0.76x10(9) L(-1) vs. 0.46, P=0.019) and CD63 (P=0.05) positive platelets compared with controls. Patients with depression also had more circulating platelet-leukocyte aggregates than controls (P<0.001). There was a positive correlation between the severity of depression and the level of platelet activation. Platelets from depressed patients were also hyperreactive to adenosine 5 -diphosphate (ADP) stimulation with increased CD62p and CD63 exposure (P=0.003 and 0.019, respectively). Six months of treatment resulted in a reduced number of circulating CD62p and CD63 positive platelets (29.84% and 53.38% decrease) and a 20.9% reduction in CD63 exposure after ADP activation. CONCLUSIONS: Depression is associated with increased in vivo platelet activation and resolution of depression using psychotherapy and/or medication reduces platelet activation. These findings provide insights into the link between depression and cardiovascular risk.