Channels and Transporters of the Pulmonary Lamellar Body in Health and Disease

The lamellar body (LB) of the alveolar type II (ATII) cell is a lysosome-related organelle (LRO) that contains surfactant, a complex mix of mainly lipids and specific surfactant proteins. The major function of surfactant in the lung is the reduction of surface tension and stabilization of alveoli during respiration. Its lack or deficiency may cause various forms of respiratory distress syndrome (RDS). Surfactant is also part of the innate immune system in the lung, defending the organism against air-borne pathogens. The limiting (organelle) membrane that encloses the LB contains various transporters that are in part responsible for translocating lipids and other organic material into the LB. On the other hand, this membrane contains ion transporters and channels that maintain a specific internal ion composition including the acidic pH of about 5. Furthermore, P2X4 receptors, ligand gated ion channels of the danger signal ATP, are expressed in the limiting LB membrane. They play a role in boosting surfactant secretion and fluid clearance. In this review, we discuss the functions of these transporting pathways of the LB, including possible roles in disease and as therapeutic targets, including viral infections such as SARS-CoV-2.

Maintenance and loss of endocytic organelle integrity: mechanisms and implications for antigen cross-presentation

The membranes of endosomes, phagosomes and macropinosomes can become damaged by the physical properties of internalized cargo, by active pathogenic invasion or by cellular processes, including endocytic maturation. Loss of membrane integrity is often deleterious and is, therefore, prevented by mitigation and repair mechanisms. However, it can occasionally be beneficial and actively induced by cells. Here, we summarize the mechanisms by which cells, in particular phagocytes, try to prevent membrane damage and how, when this fails, they repair or destroy damaged endocytic organelles. We also detail how one type of phagocyte, the dendritic cell, can deliberately trigger localized damage to endocytic organelles to allow for major histocompatibility complex class I presentation of exogenous antigens and initiation of CD8 + T-cell responses to viruses and tumours. Our review highlights mechanisms for the regulation of endocytic organelle membrane integrity at the intersection of cell biology and immunology that could be co-opted for improving vaccination and intracellular drug delivery.

Targeting Ferroptosis for Lung Diseases: Exploring Novel Strategies in Ferroptosis-Associated Mechanisms

Ferroptosis is an iron-dependent regulated necrosis characterized by the peroxidation damage of lipid molecular containing unsaturated fatty acid long chain on the cell membrane or organelle membrane after cellular deactivation restitution system, resulting in the cell membrane rupture. Ferroptosis is biochemically and morphologically distinct and disparate from other forms of regulated cell death. Recently, mounting studies have investigated the mechanism of ferroptosis, and numerous proteins play vital roles in regulating ferroptosis. With detailed studies, emerging evidence indicates that ferroptosis is found in multiple lung diseases, demonstrating that ferroptosis appears to be particularly important for lung diseases. The mounting interest in ferroptosis drugs specifically targeting the ferroptosis mechanism holds substantial therapeutic promise in lung diseases. The present review emphatically summarizes the functions and integrated molecular mechanisms of ferroptosis in various lung diseases, proposing that multiangle regulation of ferroptosis might be a promising strategy for the clinical treatment of lung diseases.

Exocytosis of the silicified cell wall of diatoms involves extensive membrane disintegration

Diatoms are unicellular algae that are characterized by their silica cell walls. The silica elements form intracellularly in a membrane-bound organelle, and are exocytosed after completion. How diatoms maintain membrane homeostasis during the exocytosis of these large and rigid silica elements is a long-standing enigma. We studied membrane dynamics during cell wall formation and exocytosis in the diatom Stephanopyxis turris, using live-cell confocal microscopy and advanced electron microscopy. Our results provide detailed information on the ultrastructure and dynamics of the silicification process, showing that during cell wall formation, the organelle membranes tightly enclose the mineral phase, creating a precise mold of the delicate geometrical patterns. Surprisingly, during exocytosis of the mature silica elements, the proximal organelle membrane becomes the new plasma membrane, and the distal membranes gradually disintegrate into the extracellular space without any noticeable endocytic retrieval or extracellular repurposing. These observations suggest that diatoms evolved an extraordinary exocytosis mechanism in order to secrete their cell wall elements.

Arginine-selective modulation of the lysosomal transporter PQLC2 through a gate-tuning mechanism

Lysosomes degrade excess or damaged cellular components and recycle their building blocks through membrane transporters. They also act as nutrient-sensing signaling hubs to coordinate cell responses. The membrane protein PQ-loop repeat-containing protein 2 (PQLC2; “picklock two”) is implicated in both functions, as it exports cationic amino acids from lysosomes and serves as a receptor and amino acid sensor to recruit the C9orf72/SMCR8/WDR41 complex to lysosomes upon nutrient starvation. Its transport activity is essential for drug treatment of the rare disease cystinosis. Here, we quantitatively studied PQLC2 transport activity using electrophysiological and biochemical methods. Charge/substrate ratio, intracellular pH, and reversal potential measurements showed that it operates in a uniporter mode. Thus, PQLC2 is uncoupled from the steep lysosomal proton gradient, unlike many lysosomal transporters, enabling bidirectional cationic amino acid transport across the organelle membrane. Surprisingly, the specific presence of arginine, but not other substrates (lysine, histidine), in the discharge (“trans”) compartment impaired PQLC2 transport. Kinetic modeling of the uniport cycle recapitulated the paradoxical substrate-yet-inhibitor behavior of arginine, assuming that bound arginine facilitates closing of the transporter’s cytosolic gate. Arginine binding may thus tune PQLC2 gating to control its conformation, suggesting a potential mechanism for nutrient signaling by PQLC2 to its interaction partners.

The PKD-Dependent Biogenesis of TGN-to-Plasma Membrane Transport Carriers

Membrane trafficking is essential for processing and transport of proteins and lipids and to establish cell compartmentation and tissue organization. Cells respond to their needs and control the quantity and quality of protein secretion accordingly. In this review, we focus on a particular membrane trafficking route from the trans-Golgi network (TGN) to the cell surface: protein kinase D (PKD)-dependent pathway for constitutive secretion mediated by carriers of the TGN to the cell surface (CARTS). Recent findings highlight the importance of lipid signaling by organelle membrane contact sites (MCSs) in this pathway. Finally, we discuss our current understanding of multiple signaling pathways for membrane trafficking regulation mediated by PKD, G protein-coupled receptors (GPCRs), growth factors, metabolites, and mechanosensors.

Effect of Composite Nanoparticle CeO2 on Myocardial Ischemic Re-Infusion of Cardio Myocyte Apoptosis in Mouse

The myocardial I/R damage is very complicated. Apoptosis is considered to its a critical mechanism. During the cardiac muscle I/R process, oxygen-free radicals play a pivotal role. Arrhythmias, as well as enlargement of the area of myocardial infarction after cardiac muscle I/R process, are caused by adequate blast generated O2- ion free radicals. During the ischemia-reperfusion process, a large amount of O2- ion free radicals destroyed the cell structure, and it undergoes lipid peroxidation with unsaturated fatty acids that contain a large number of phospholipids in the cell membrane, causing membrane proteins such as ion channels and enzymes on the cell membrane. The activity of cell is reduced, which affects the function of cell membrane and organelle membrane, destroys its integrity and reduces fluidity.We observed the effects of cerium dioxide nanoparticles on glutathione peroxidase as well as superoxide dismutase, also propionate in myocardial tissue of I/R injury in the mouse. Its effects of malondialdehyde and apoptosis were explored to see its protective effect and to provide more preventive measures for ischemia-reperfusion injury.