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Introduction to Cancer, Conventional Therapies, and Bionano-Based Advanced Anticancer Strategies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
It is a self-digestion process, which is also another source of cell death. It is the process where it removes and degrades the damaged cellular constituents by which a small portion of cellular components are isolated from the rest of the cell to form a double layered vesicle called autophagosome. Autophagosome further fuses with lysosome having low pH (acidic) and later endosome to form autolysosome. When autophagy and lysosome degradation is disturbed, Cathespin B is released from lysosome to trigger mitochondrial permeabalization and caspase activation. Cathespin D is translocated from lysosome to cytosol, which is responsible for Bax activation and apoptotic induced factor release. In addition, caspase cleave autophagy relative proteins, such as Beclin1, Bcl-2, P53, and UV-irradiation resistance gene (UVRAG), are several tumor proteins that regulate autophagy.
Lysosomal Ion Channels and Human Diseases
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Peng Huang, Mengnan Xu, Yi Wu, Xian-Ping Dong
Autophagy is a lysosome-dependent cellular process for the turnover of organelles and molecules. It is predominantly a cell-survival mechanism, playing a critical role in cell growth, cell proliferation and differentiation, and tissue homeostasis and development (Klionsky et al., 2016; Levine and Kroemer, 2008; Mizushima and Levine, 2010). Cellular stress conditions such as nutrient and energy deprivation and diseases elevate autophagy. During autophagy, cytoplasmic components are engulfed by autophagosomes that fuse with lysosomes where cytoplasmic components are degraded by lysosomal hydrolases and then recycled. Autophagic flux is regulated by a series of events, including autophagy initiation, autophagosome-lysosome fusion (autophagosome maturation), autolysosome degradation, and lysosome reformation (Klionsky et al., 2016; Yu et al., 2010). Disruption of any of them could lead to impaired autophagy that has been associated with abnormalities such as LSDs, neurodegeneration, cancer, and inflammatory, infectious and autoimmune conditions (Fulda and Kogel, 2015; Hara et al., 2006; Komatsu et al., 2006; Levine and Kroemer, 2008; Levine et al., 2011). Basal autophagy is especially important in postmitotic cells such as neurons and muscles, where the accumulation of aggregated proteins and damaged organelles often results in cell death (Hara et al., 2006; Komatsu et al., 2006; Levine and Kroemer, 2008). Indeed, the suppression of basal autophagy causes neurodegeneration (Hara et al., 2006; Komatsu et al., 2006) and myofiber degeneration and weakness (Masiero et al., 2009; Raben et al., 2008).
Etiopathogenesis
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Dario Didona, Biagio Didona, Giovanni Paolino, Raffaele Dante Caposiena Caro
Both micro- and macro-autophagy are involved in engulfing large structures through both selective and nonselective mechanisms. On the other hand, CMA degrades only soluble proteins in a selective way [32]. In macro-autophagy, a multimembrane structure known as a phagophore engulfs the cytoplasmic organelles, producing a vesicular structure called an autophagosome. Subsequently, the autophagosome fuses with the lysosome, forming a single membrane structure called an autolysosome [31]. On the other hand, micro-autophagy is characterized by direct engulfing of organelles, involving a process of invaginating, protrusion, and/or septation of the lysosomal-limiting membrane [32]. Instead, CMA involves the 70 KDa heat shock-cognate protein and the lysosomal-associated membrane protein 2A receptor (LAMP2A) to transport specific cytosolic proteins, all characterized by pentapeptide sequence Lys-Phe-Gln-Arg-Gln, into lysosomes [32].
Bone-targeted nanoplatform enables efficient modulation of bone tumor microenvironment for prostate cancer bone metastasis treatment
Published in Drug Delivery, 2022
Xiangyu Zhang, Qingbin Liu, Tingting Zhang, Pei Gao, Hui Wang, Lu Yao, Jingwen Huang, Shulong Jiang
First of all, PC-3 cells were treated with DTXL or siRNA drugs, then cells were transfected with mRFP-GFP-LC3 lentivirus for 8 h, and the autophagic flux was examined by fluorescence microscopy. As the green fluorescence of the GFP did not appear at the autolysosomes, the red puncta indicate the autolysosome. The (DTXL + siRNA)@NPs-ALN group showed considerably more red puncta compared with other groups, indicating that the autolysosome increased in this group when compared with other groups (Figures 6(A,B)). This result was further confirmed by TEM observation of the autolysosome, which was consistent with the fluorescence microscopy results, revealed that the (DTXL + siRNA)@NPs-ALN treatment dramatically increased the number of autolysosomes (Figures 6(C,D)). Consistent with the fluorescence results and TEM results, the LC3-II was upregulated and the p62 protein was downregulated in the (DTXL + siRNA)@NPs-ALN group, autophagy was effectively induced in this group (Figure 3(C)).
Acrylamide induces intrinsic apoptosis and inhibits protective autophagy via the ROS mediated mitochondrial dysfunction pathway in U87-MG cells
Published in Drug and Chemical Toxicology, 2022
Linlin Deng, Mengyao Zhao, Yanan Cui, Quanming Xia, Lihua Jiang, Hao Yin, Liming Zhao
Considering the known association between oxidative stress and autophagy, this study investigated whether cell autophagy promoted the progression of ACR-induced cell death. ACR regulated U87-MG cellular autophagic signaling by increasing the P62 and Beclin1 expression while decreasing the LC3 I/LC3 II ratio in protein expression. Moreover, TEM observation revealed an increase in autophagosome formation and autolysosome accumulation. Considering autophagic flux appears to denote a new strategy while investigating the cell death mechanism. The results showed that ACR likely inhibited autophagic flux since it restricted autophagosome and lysosome fusion, which were consistent with the findings obtained via CQ treatment by transfecting the GFP-RFP-LC3 adenoviruses and co-localization immunofluorescence. Accordingly, Yan et al. (2018) indicated that ACR inhibited lysosomal protease (cathepsin D), blocking the autophagic lysosomal degradation pathway and ultimately causing spatial memory impairment in a mice model (Yan et al. 2018). Song et al. (2021) revealed that ACR induced LC3-II and p62 accumulation in U2OS cells (Song et al. 2021).
Mitochondria autophagy: a potential target for cancer therapy
Published in Journal of Drug Targeting, 2021
Yu-Han Qiu, Tian-Shu Zhang, Xiao-Wei Wang, Meng-yan Wang, Wen-Xia Zhao, Hui-Min Zhou, Cong-Hui Zhang, Mei-Lian Cai, Xiao-Fang Chen, Wu-Li Zhao, Rong-Guang Shao
Mitochondria are double-membrane organelles and are the most important organelles supplying energy for cell survival. Defects in mitochondrial functions not only affect cellular homeostasis, bioenergetics and redox control but also control cell survival [5]. Due to their abundance and sensitivity to the external environment, mitochondria are easily targeted by drugs and damaged in response to stimulation by reactive oxygen species (ROS), nutrient deficiency and cellular senescence. When the damage is slight or moderate, autophagy is induced to remove the damaged or dysfunctional mitochondria in order to maintain cellular homeostasis. If mitochondria are severely damaged, they are destroyed, and cytochrome C is released to trigger apoptosis [6]. During mitophagy, first, the mitochondrial membrane is depolarised and a phagophore is formed; then, the bilayer membrane of the phagophore continues to expand and extend to wrap the damaged mitochondria in the cytoplasm and form an autophagosome. Finally, the formed autophagosome fuses with a lysosome to form an autolysosome. The enclosed contents are degraded, and mitophagy is completed.