Endosomal and Lysosomal Electrophysiology
Bruno Gasnier, Michael X. Zhu in Ion and Molecule Transport in Lysosomes, 2020
This chapter describes detailed protocols of endosomal and lysosomal electrophysiology and discusses several examples of lysosomal channels that have been characterized using patch-clamp method. Dysregulation of lysosomal ion flux leads to a lysosome storage phenotype with the characteristic accumulation of enlarged vacuoles, cellular wastes, and lipofuscin in the cell. The mechanistic target of rapamycin, the primary nutrient sensor in the cell, is found to be localized on the lysosomal membrane to regulate various lysosomal functions. Lysosomal channels represent promising therapeutic targets for lysosomal diseases. Lysosomal ion homeostasis is established and maintained by lysosomal ion channels and transporters that mediate ionic flux across the lysosomal membranes in response to various cellular cues that are derived from either the cytoplasm or the lysosome lumen. Transient receptor potential channel mucolipin-1 is also a lysosomal sensor of reactive oxygen species that is required for lysosomal adaptation to oxidative stress.
Lysosomal Ion Channels and Human Diseases
Long-Jun Wu in Nonclassical Ion Channels in the Nervous System, 2021
Ion channels are a group of proteins residing in both the plasma membrane and intracellular membranes. Their opening allows the passage of ions from one side of the membrane to the other following the electrochemical gradient. The physiology and functions of ion channels in the plasma membrane have been extensively studied. Because of the inaccessibility of intracellular membranes, our understanding of organellular ion channels is largely hampered. However, new developments in biomedical methodology in recent years have made it possible to investigate intracellular ion channels. In this chapter, we provide a summary of newly identified ion channels in the lysosome. The characteristics, physiological functions, and pathological roles of these ion channels are discussed. We hope to guide the readers into a more in-depth discussion of the importance of lysosomal ion channels in cellular functions and human diseases.
Structure and function of skin
Roger L. McMullen in Antioxidants and the Skin, 2018
This chapter attempts to cover some of the fundamental concepts involving the structure and function of skin. It discusses the Skin Immune System and various cells associated with the immune response are found. Morphologically, the skin is composed of two principal components, the epidermis and dermis, which contain various cell types and structural proteins. The stratum basale is the lowest layer in the epidermis and consists of a single layer of cells, which are predominantly keratinocytes. In this part of the epidermis, the keratinocytes are undifferentiated and contain all of the usual organelles that are present in viable cells, such as mitochondrion, Golgi apparatus, ribosome, endoplasmic reticulum, lysosome, and nucleus. The primary cell types present in the dermis include fibroblasts, mast cells, and tissue macrophages. Fibroblasts are the most abundant cell type and are responsible for the synthesis and structuring of the structural tissue and ground substance.
The Roles of Lysosomes in Inflammation and Autoimmune Diseases
Published in International Reviews of Immunology, 2015
Wei Ge, Dongxu Li, Yanpan Gao, Xuetao Cao
Lysosomes perform a range of functions, some of which, such as degradation, are common to all cell types. Others, such as secretion or lysosomal exocytosis, are more specialised and tend to involve fusion of this organelle with the cell surface to release its contents. This review describes lysosomal regulation of the inflammatory glucocorticoid signaling pathways, and summarizes the roles of lysosomes in negatively or positively modulating the production of inflammatory cytokines. We also review the characteristic changes in lysosomal hydrolases and membrane proteins in common autoimmune diseases. Finally, future directions in lysosome research are proposed, with it being suggested that the role of lysosomes will continue to be of growing interest in immunity research.
Pompe disease: Shared and unshared features of lysosomal storage disorders
Published in Rare Diseases, 2015
Jeong-A Lim, Or Kakhlon, Lishu Li, Rachel Myerowitz, Nina Raben
Pompe disease, an inherited deficiency of lysosomal acid α-glucosidase (GAA), is a severe metabolic myopathy with a wide range of clinical manifestations. It is the first recognized lysosomal storage disorder and the first neuromuscular disorder for which a therapy (enzyme replacement) has been approved. As GAA is the only enzyme that hydrolyses glycogen to glucose in the acidic environment of the lysosome, its deficiency leads to glycogen accumulation within and concomitant enlargement of this organelle. Since the introduction of the therapy, the overall understanding of the disease has progressed significantly, but the pathophysiology of muscle damage is still not fully understood. The emerging complex picture of the pathological cascade involves disturbance of calcium homeostasis, mitochondrial abnormalities, dysfunctional autophagy, accumulation of toxic undegradable materials, and accelerated production of lipofuscin deposits that are unrelated to aging. The relationship of Pompe disease to other lysosomal storage disorders and potential therapeutic interventions for Pompe disease are discussed.
The yeast protein sorting pathway as an experimental model for lysosomal trafficking
Published in Expert Review of Clinical Immunology, 2007
Marta Hoffman-Sommer, Joanna Rytka
Lysosomes are conserved organelles that are present in all eukaryotic cells. They are part of a complicated network of intracellular trafficking routes – the lysosomal transport system. Lysosomes are necessary for the maintenance of cellular homeostasis and for many specialized functions, including the activity of many components of the mammalian immune system. Dysfunctions of the lysosomal system are associated with numerous diseases, such as storage disorders, neuro- and myopathies, cancer and some types of albinism and immunological deficiencies. High conservation of the processes of lysosomal biogenesis and transport enables the use of yeast as a model for studying the mechanisms that underlie these diseases. In this review, we discuss several examples of such models in an attempt to present an overview of the most important experimental methods available in yeast research.
Related Knowledge Centers
- Fertilization
- Fetus
- Membrane Fusion
- Insulin
- Sperm Head
- Cytoplasmic Vesicles
- Blood Sugar