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Biogenesis and Functional Roles of Lysosomes: Their Implications for the Pathogenesis and Therapy of Human Diseases 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 15531

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Special Issue Information

Dear Colleagues,

The Special Issue that was launched last year successfully collected fourteen articles in less than one year. Given the interest raised by the topic, we have decided to launch a second volume of this Special Issue dedicated to the biology and pathophysiology of lysosomes. We have included an additional topic dedicated to the involvement of lysosomes in microbial infections, which shall attract research focused on the role of acidic compartments in intracellular duplication or killing of viruses and bacteria.

The lysosome is the most acidic compartment ubiquitously present in eukaryotic cells. Christian De Duve was awarded the Nobel Prize for having discovered this organelle in the early sixties. Since then, we have learned lots about the biogenesis and function of this organelle and of its related companions. Initially defined as a “suicide bag” or “waste bin”, the lysosome has gained a noble reputation in recent decades as an organelle playing critical roles in cell death and survival and, by extension, in tissue homeostasis. The array of acidic hydrolases present in the lysosome endows this organelle with the ability to digest almost all the biomolecules delivered into it. Accordingly, the lack of a lysosomal enzyme would result in the abnormal accumulation of undigested substrate and a consequent lack of downstream products. Lysosome and lysosome-related organelles, which comprise early and late endosomes, constitute a dynamic network of vesicles that traffic and process substrates coming from inside and outside through the connection with the autophagy and endocytosis processes, respectively. In addition, the endosomal–lysosomal system is also involved in cell-to-cell communication through the exocytosis pathway and the release of exosomes, which are generated within the late endosomes. Specialized lysosome-related organelles are present in highly differentiated cells where these organelles accomplish unique functions. From the above, it appears clear that defective biogenesis or malfunctioning of this organelle would negatively impact human health. This Special Issue will collect either research or review articles addressing the biogenesis and pathophysiological role of lysosome and lysosome-related organelles in human health and disease.

Topics include but are not limited to the following:

  • Biogenesis of acidic compartments and their function in cells;
  • Trafficking of molecules and membranes among endosomal–lysosomal organelles;
  • Endocytosis and exocytosis in cell communication;
  • Biogenesis and function of exosomes;
  • Lysosomes in cell survival and cell death pathways;
  • Lysosomes and autophagy;
  • Lysosomes in development and embryomorphogenesis;
  • Dysfunctional lysosomes in human pathologies, with a special focus on autoimmune diseases, neurodegenerative diseases, lysosomal storage diseases, and cancer;
  • Lysosomes as a therapeutic target in human diseases;
  • Replacement gene therapy for lysosome dysfunction;
  • Lysosomal proteins as disease markers;
  • Lysosomes and microbial infections.

Prof. Dr. Ciro Isidoro
Guest Editor

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Keywords

  • Lysosome
  • Endosomes
  • Exosome
  • Cell homeostasis
  • Autophagy
  • Cell death
  • Therapy
  • Disease
  • Development
  • Lysosomal enzymes

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Related Special Issue

Published Papers (3 papers)

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Research

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19 pages, 1697 KiB  
Article
High Expression of the Lysosomal Protease Cathepsin D Confers Better Prognosis in Neuroblastoma Patients by Contrasting EGF-Induced Neuroblastoma Cell Growth
by Eleonora Secomandi, Amreen Salwa, Chiara Vidoni, Alessandra Ferraresi, Carlo Follo and Ciro Isidoro
Int. J. Mol. Sci. 2022, 23(9), 4782; https://doi.org/10.3390/ijms23094782 - 26 Apr 2022
Cited by 4 | Viewed by 2273
Abstract
Neuroblastoma is a malignant extracranial solid tumor arising from the sympathoadrenal lineage of the neural crest and is often associated with N-MYC amplification. Cathepsin D has been associated with chemoresistance in N-MYC-overexpressing neuroblastomas. Increased EGFR expression also has been associated with the aggressive [...] Read more.
Neuroblastoma is a malignant extracranial solid tumor arising from the sympathoadrenal lineage of the neural crest and is often associated with N-MYC amplification. Cathepsin D has been associated with chemoresistance in N-MYC-overexpressing neuroblastomas. Increased EGFR expression also has been associated with the aggressive behavior of neuroblastomas. This work aimed to understand the mechanisms linking EGFR stimulation and cathepsin D expression with neuroblastoma progression and prognosis. Gene correlation analysis in pediatric neuroblastoma patients revealed that individuals bearing a high EGFR transcript level have a good prognosis only when CTSD (the gene coding for the lysosomal protease Cathepsin D, CD) is highly expressed. Low CTSD expression was associated with poor clinical outcome. CTSD expression was negatively correlated with CCNB2, CCNA2, CDK1 and CDK6 genes involved in cell cycle division. We investigated the biochemical pathways downstream to EGFR stimulation in human SH-SY5Y neuroblastoma cells engineered for overexpressing or silencing of CD expression. Cathepsin D overexpression decreased the proliferative potential of neuroblastoma cells through downregulation of the pro-oncogenic MAPK signaling pathway. EGFR stimulation downregulated cathepsin D expression, thus favoring cell cycle division. Our data suggest that chemotherapeutics that inhibit the EGFR pathway, along with stimulators of cathepsin D synthesis and activity, could benefit neuroblastoma prognosis. Full article
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Review

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24 pages, 2424 KiB  
Review
Role of Ceramides and Lysosomes in Extracellular Vesicle Biogenesis, Cargo Sorting and Release
by Rostyslav Horbay, Ali Hamraghani, Leonardo Ermini, Sophie Holcik, Shawn T. Beug and Behzad Yeganeh
Int. J. Mol. Sci. 2022, 23(23), 15317; https://doi.org/10.3390/ijms232315317 - 5 Dec 2022
Cited by 22 | Viewed by 6137
Abstract
Cells have the ability to communicate with their immediate and distant neighbors through the release of extracellular vesicles (EVs). EVs facilitate intercellular signaling through the packaging of specific cargo in all type of cells, and perturbations of EV biogenesis, sorting, release and uptake [...] Read more.
Cells have the ability to communicate with their immediate and distant neighbors through the release of extracellular vesicles (EVs). EVs facilitate intercellular signaling through the packaging of specific cargo in all type of cells, and perturbations of EV biogenesis, sorting, release and uptake is the basis of a number of disorders. In this review, we summarize recent advances of the complex roles of the sphingolipid ceramide and lysosomes in the journey of EV biogenesis to uptake. Full article
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26 pages, 1914 KiB  
Review
The Endolysosomal System: The Acid Test for SARS-CoV-2
by Daniella Cesar-Silva, Filipe S. Pereira-Dutra, Ana Lucia Moraes Giannini and Cecília Jacques G. de Almeida
Int. J. Mol. Sci. 2022, 23(9), 4576; https://doi.org/10.3390/ijms23094576 - 20 Apr 2022
Cited by 8 | Viewed by 6067
Abstract
This review aims to describe and discuss the different functions of the endolysosomal system, from homeostasis to its vital role during viral infections. We will initially describe endolysosomal system’s main functions, presenting recent data on how its compartments are essential for host defense [...] Read more.
This review aims to describe and discuss the different functions of the endolysosomal system, from homeostasis to its vital role during viral infections. We will initially describe endolysosomal system’s main functions, presenting recent data on how its compartments are essential for host defense to explore later how SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) and other coronaviruses subvert these organelles for their benefit. It is clear that to succeed, pathogens’ evolution favored the establishment of ways to avoid, escape, or manipulate lysosomal function. The unavoidable coexistence with such an unfriendly milieu imposed on viruses the establishment of a vast array of strategies to make the most out of the invaded cell’s machinery to produce new viruses and maneuvers to escape the host’s defense system. Full article
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