Metformin induces iron deprivation and enhances mitochondrial ROS in macrophages creating a hostile environment for survival of intracellular Mycobacterium tuberculosis.

Diabetes, especially type 2 diabetic mellitus (T2DM) is associated with increased risk of contracting tuberculosis (TB). Though several factors, including immune system dysfunction, have been linked to this sensitivity the exact reasons have yet to be fully elucidated. Although metformin, a diabetic medication, has been suggested as a potential supplementary for host-directed therapy of tuberculosis, the mechanisms of its anti-TB effects remain unclear.

Mycobacterium tuberculosis exploits SIRT2 to trap iron for its intracellular survival.

Iron is a critical nutrient for all organisms ranging from bacteria to humans. Ensuring control of this strategic vital resource significantly influences the dynamics of the struggle between host and invading pathogen. Mycobacterium tuberculosis (Mtb), the causative agent of the pulmonary disease tuberculosis (TB), has been plaguing humans for millennia and has evolved to successfully persist and multiply within host cells evading the mammalian immune defences.

Chronic hyperglycemia impairs anti-microbial function of macrophages in response to Mycobacterium tuberculosis infection.

Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB), though the underlying mechanisms linking DM and TB remain ambiguous. Macrophages are a key player in the innate immune response and their phagocytic ability is enhanced in response to microbial infections. Upon infection or inflammation, they also repel invading pathogens by generating; reactive oxygen species (ROS), reactive nitrogen species (RNS), pro-inflammatory cytokines (IL-1β and IL-6), and anti-inflammatory cytokines (IL-10).

Glyceraldehyde-3-Phosphate Dehydrogenase Binds with Spike Protein and Inhibits the Entry of SARS-CoV-2 into Host Cells.

Introduction: Coronavirus disease 2019 caused by coronavirus-2 (SARS-CoV-2) has emerged as an aggressive viral pandemic. Health care providers confront a challenging task for rapid development of effective strategies to combat this and its long-term after effects. Virus entry into host cells involves interaction between receptor-binding domain (RBD) of spike (S) protein S1 subunit with angiotensin converting enzyme present on host cells.

Excess iron aggravates the severity of COVID-19 infection.

Coronavirus disease-19 (COVID-19) can induce severe inflammation of the lungs and respiratory system. Severe COVID-19 is frequently associated with hyper inflammation and hyper-ferritinemia. High iron levels are known to trigger pro-inflammatory effects.

Regulation of Macrophage Cell Surface GAPDH Alters LL-37 Internalization and Downstream Effects in the Cell.

Mycobacterium tuberculosis (M.tb), the major causative agent of tuberculosis, has evolved mechanisms to evade host defenses and persist within host cells. Host-directed therapies against infected cells are emerging as an effective option.

Exposure of a specific pleioform of multifunctional glyceraldehyde 3-phosphate dehydrogenase initiates CD14-dependent clearance of apoptotic cells.

Rapid clearance of apoptotic cells by phagocytes is crucial for organogenesis, tissue homeostasis, and resolution of inflammation. This process is initiated by surface exposure of various 'eat me' ligands. Though phosphatidylserine (PS) is the best recognized general recognition ligand till date, recent studies have shown that PS by itself is not sufficient for clearance of apoptotic cells.

Glyceraldehyde-3-Phosphate Dehydrogenase Facilitates Macroautophagic Degradation of Mutant Huntingtin Protein Aggregates.

Protein aggregate accumulation is a pathological hallmark of several neurodegenerative disorders. Autophagy is critical for clearance of aggregate-prone proteins. In this study, we identify a novel role of the multifunctional glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in clearance of intracellular protein aggregates.

Moonlighting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) modulates protein aggregation.

Onset of protein aggregation reflects failure of the cellular folding machinery to keep aggregation-prone protein from misfolding and accumulating into a non-degradable state. FRET based analysis and biochemical data reveal that cytosolic prion (cyPrP) and httQ-103 interact with the multifunctional protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) leading to few detectable aggregates in GAPDH-over expressing cells.The preventive effect of GAPDH suggests that this abundant and long-lived cytoplasmic protein has an active role in the shielding and maintenance, in soluble form of proteins as heterogeneous as huntingtin and cyPrP.