TRPML Subfamily of Endolysosomal Channels
Bruno Gasnier, Michael X. Zhu in Ion and Molecule Transport in Lysosomes, 2020
The mucolipin subgroup of the transient receptor potential superfamily of cation channels (TRPMLs) are evolutionarily conserved non-selective cation channels that function in endolysosomal membranes, and play key roles in the regulation of endocytosis, autophagy, and intracellular trafficking. The lack of effective antibodies against TRPMLs, which is exacerbated by the low expression levels of these proteins, has hindered detailed examination of their tissue and subcellular distribution. Consequently, most studies investigating the location of these channels across tissues rely on mRNA quantification. The endocytic pathway is initiated at the plasma membrane, where molecularly defined regions of the bilayer are pinched inwards to form early endosomes via a pathway orchestrated with exquisite spatiotemporal precision. The purpose of the following sections is to provide an overview of some of the tools and resources that may be used to study the localization, trafficking, and channel function of TRPMLs.
Approach to Vacuolar Myopathy
Maher Kurdi in Neuromuscular Pathology Made Easy, 2021
Cytoplasmic vacuoles are a frequent feature in numerous neuromuscular disorders. The terms vacuolar myopathy and autophagic vacuolar myopathy are commonly used in muscle pathology practice referring to a group of muscle diseases characterized by myopathic features and vacuolations. These vacuoles are always autophagic in nature and vary in their contents and appearance. It has been scientifically proven that autophagic dysfunction during the cellular catabolic process is considered the main predisposing factor for vacuolar myopathy. This dysfunction prevents the elimination of misfolded protein aggregates and increases the ability of cellular oxidative stress. As a result, lysosomal breakdown occurs. Several mechanisms in the literature have explained the pathogenesis of these vacuoles. In this chapter, we describe the different types of cytoplasmic vacuoles and their clinical significance in differential diagnosis.
Mechanistic Aspects of Neurodegeneration in Alzheimer’s Disease and the Role of Phytochemicals as Restorative Agents
Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu in Phytomedicine and Alzheimer’s Disease, 2020
Alzheimer’s disease is a complex, multifactorial, irreversible, progressive, neurodegenerative disorder, which gradually destroys cognitive performances, eventually increasing the restrictions on daily activities and the dependency. The development of advanced statistical models for analysis of large, multimodal data sets will assist in the exploration of potentially new paradigms. A wide variety of stimuli and conditions, both physiological and pathological, can initiate apoptosis as a defense mechanism. Autophagy is a lysosome-degradative process, dealing with maintaining homeostasis or normal cell function by protein degradation and turnover of damaged cell organelles, to achieve new cell synthesis. The internalization and subsequent endosomal trafficking of proteins and membranes along the endocytic pathway is a fundamental cellular process. Homophilic and heterophilic adhesion of cells in the brain can be initiated in an integrated, conventional manner to perform a significant and precise structural role through the specialized junctions, consisting of clustered cell adhesion molecules.
Autophagy, cell death, and cancer
Published in Molecular & Cellular Oncology, 2015
Autophagy is an evolutionarily conserved intracellular catabolic process that is used by all cells to degrade dysfunctional or unnecessary cytoplasmic components through delivery to the lysosome. Increasing evidence reveals that autophagic dysfunction is associated with human diseases, such as cancer. Paradoxically, although autophagy is well recognized as a cell survival process that promotes tumor development, it can also participate in a caspase-independent form of programmed cell death. Induction of autophagic cell death by some anticancer agents highlights the potential of this process as a cancer treatment modality. Here, we review our current understanding of the molecular mechanism of autophagy and the potential roles of autophagy in cell death, cancer development, and cancer treatment.
Chitosan nanoparticles triggered the induction of ROS-mediated cytoprotective autophagy in cancer cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Hao Wang, Xiwei Yu, Chang Su, Yijie Shi, Liang Zhao
There is a close relationship between autophagy and apoptosis during cancer cell death. We used chitosan nanoparticles (CS NPs) to explore the effects of internalized NPs on the induction of autophagy and to confirm the role of autophagic responses elicited by nanomaterials on the tumour cell’s fate. CS NPs at nontoxic concentrations ranging from 10–100 μg/mL triggered the induction of autophagy. With the addition of CS NPs, the aggregation of endogenous LC3 was significantly enhanced and acidic autophagic bodies had been accumulated. CS NPs significantly triggered the occurrence of autophagy by increasing the ratio of LC3 II to LC3 I and CS NPs-mediated autophagy was implicated in reactive oxygen species (ROS) generation and the ROS scavenger N-acetylcysteine (NAC) attenuated CS-induced autophagy. The addition of blank NPs produced a negative effect on cytotoxicity and cellular apoptosis of free Dox, and with the pre-treatment of chloroquine (CQ) as a known autophagy inhibitor, the inhibition rates of cells treated with the combination of Dox and blank CS NPs had been significantly increased. The findings demonstrated that CS NPs have the ability to induce protective autophagy via ROS generation and they were believed to inhibit tumour cell death.
Aggressive human neuroblastomas show a massive increase in the numbers of autophagic vacuoles and damaged mitochondria
Published in Ultrastructural Pathology, 2016
Gordana Samardzija, Tamara Kravic Stevovic, Slavisa Djuricic, Dragomir Djokic, Marina Djurisic, Darko Ciric, Tamara Martinovic, Vladimir Bumbasirevic, Dragana Vujic
Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs.
Related Knowledge Centers
- Mitochondria
- Neurodegenerative Diseases
- Biological Metamorphosis
- Vacuoles
- Hspa
- Assisted
- Lamp