An association between mitochondria and microglia effector function: what do we think we know?

While resident innate immune cells of the central nervous system, the microglia, represent a cell population unique in origin, microenvironment, and longevity, they assume many properties displayed by peripheral macrophages. One prominent shared property is the ability to undergo a metabolic switch towards glycolysis and away from oxidative phosphorylation (OXPHOS) upon activation by the pro-inflammatory stimuli lipopolysaccharide. This shift serves to meet specific cellular demands and allows for cell survival, similar to the Warburg effect demonstrated in cancer cells. In contrast, normal surveillance phenotype or stimulation to a non-proinflammatory phenotype relies primarily on OXPHOS and fatty acid oxidation. Thus, mitochondria appear to function as a pivotal signaling platform linking energy metabolism and macrophage polarization upon activation. These unique shifts in cell bioenergetics in response to different stimuli are essential for proper effector responses at sites of infection, inflammation, or injury. Here, we present a summary of recent developments as to how these dynamics characterized in peripheral macrophages are displayed in microglia. The new insights provided by an increased understanding of metabolic reprogramming in macrophages may allow for translation to the central nervous system and a better understanding of microglia heterogeneity, regulation, and function

Adhesion of Blood Plasma Proteins and Platelet-rich Plasma on <i><i>l</i></i>‑Valine-Based Poly(ester urea)

The competitive absorption of blood plasma components including fibrinogen (FG), bovine serum albumin (BSA), and platelet-rich plasma (PRP) on <i><i>l</i></i>-valine-based poly­(ester urea) (PEU) surfaces were investigated. Using four different PEU polymers, possessing compositionally dependent trends in thermal, mechanical, and critical surface tension measurements, water uptake studies were carried out to determine <i>in vitro</i> behavior of the materials. Quartz crystal microbalance (QCM) measurements were used to quantify the adsorption characteristics of PRP onto PEU thin films by coating the surfaces initially with FG or BSA. Pretreatment of the PEU surfaces with FG inhibited the adsorption of PRP and BSA decreased the absorption 4-fold. <i>In vitro</i> studies demonstrated that cells cultured on <i><i>l</i></i>-valine-based PEU thin films allowed attachment and spreading of rat aortic cells. These measurements will be critical toward efforts to use this new class of materials in blood-contacting biomaterials applications

CHIP regulates aquaporin-2 quality control and body water homeostasis

The importance of the kidney distal convoluted tubule (DCT) and cortical collecting duct (CCD) is highlighted by various water and electrolyte disorders that arise when the unique transport properties of these segments are disturbed. Despite this critical role, little is known about which proteins have a regulatory role in these cells and how these cells can be regulated by individual physiologic stimuli. By combining proteomics, bioinformatics, and cell biology approaches,we found that the E3 ubiquitin ligase CHIP is highly expressed throughout the collecting duct; is modulated in abundance by vasopressin; interacts with aquaporin-2 (AQP2), Hsp70, and Hsc70; and can directly ubiquitylate the water channel AQP2 in vitro. shRNA knockdown of CHIP in CCD cells increased AQP2 protein t 1/2 and reduced AQP2 ubiquitylation, resulting in greater levels of AQP2 andphosphorylatedAQP2.CHIP knockdown increased the plasma membrane abundance of AQP2 in these cells. Compared with wild-type controls, CHIP knockout mice or novel CRISPR/Cas9 mice without CHIPE3 ligase activity had greater AQP2 abundance and altered renal water handling, with decreased water intake and urine volume, alongside higher urine osmolality. We did not observe significant changes in other water- or sodium-transporting proteins in the gene-modified mice. In summary, these results suggest that CHIP regulates AQP2 and subsequently, renal water handling