Metabolism
MAP4K3 inhibits Sirtuin-1 to repress the LKB1–AMPK pathway to promote amino acid-dependent activation of the mTORC1 complexOur results reveal the existence of a novel signaling pathway linking amino acid satiety with MAP4K3-dependent suppression of SIRT1 to inactivate the repressive LKB1–AMPK pathway and thereby potently activate the mTORC1 complex to dictate the metabolic disposition of the cell.
Cognitive decline in diabetic mice predisposed to Alzheimer’s disease is greater than in wild typeThis work proposes that T2DM is particularly harmful to brain function in individuals with a genetic predisposition to neurodegenerative pathology via, among others, γ-secretase inhibition.
Proteomic analysis reveals microvesicles containing NAMPT as mediators of radioresistance in gliomaGlioma patients often relapse because of resistance to radiation therapy. The transfer of the metabolic enzyme NAMPT via microvesicles and the accompanying elevated levels of NAD are found to be a mechanism by which glioma cells become resistant to radiation.
An OMA1 redox site controls mitochondrial homeostasis, sarcoma growth, and immunogenicityThis work describes how a mutation affecting mitochondrial metabolism in a sarcoma model induces protective immunity against the tumor and how this result might be relevant for sarcoma patients.
A novel approach to measure complex V ATP hydrolysis in frozen cell lysates and tissue homogenatesThis novel method can be used in clinical samples to determine CV function in diseases, with the added benefit of being able to use frozen samples in a high-throughput manner and to explore ATP hydrolysis as a drug target for disease treatment.
Cardiac Plin5 interacts with SERCA2 and promotes calcium handling and cardiomyocyte contractilityWe show that elevated cardiac Plin5 correlates with up-regulation of cardiac contraction–related processes, unraveling a novel Plin5 interaction with SERCA2 associated with improved calcium handling.
ZBTB18 inhibits SREBP-dependent lipid synthesis by halting CTBPs and LSD1 activity in glioblastomaThis study identifies a new mechanism of fatty acid synthesis regulation in glioblastoma that involves ZBTB18, CTBP, and LSD1. The transcriptional repressor ZBTB18 interacts with CTBP and inhibits LSD1 demethylase activity.
Hepatic DKK1-driven steatosis is CD36 dependentIncreased DKK1 in hepatic steatosis contributes CD36-mediated fatty acid uptake and insulin resistance.
Palmitate impairs circadian transcriptomics in muscle cells through histone modification of enhancersThe disruption of circadian rhythms because of lipid overload may lead to epigenomic changes that influence metabolism. Thus, a dietary or therapeutic modulation of lipid levels, a cornerstone in the treatment of metabolic disorders, may prevent circadian misalignment in peripheral tissues.
A high-content endogenous GLUT4 trafficking assay reveals new aspects of adipocyte biologyThe authors describe a high-throughput method for measuring endogenous GLUT4 and transferrin receptor translocation in adipocytes. They reveal that this method has advantages over studying GLUT4 trafficking using overexpressed GLUT4 reporters, which are commonly used in the field.