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Mitochondrial Dysfunction in Huntington Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Md. Hafiz Uddin, Marufa Rumman, Tasnuva Sarowar
The lack of balance between mitochondrial fission and fusion negatively affects mitochondrial turnover. Autophagy, as previously referred, is an important intracellular mechanism that removes damaged organelles and misfolded/aggregated proteins to maintain cell homeostasis (Carvalho et al. 2015). Autophagy is characterized by the presence of autophagic vacuoles, autophagosomes (Kamat et al. 2014). An optimal level of autophagy is essential for recycling cellular organelles, which provides neuroprotection. However, increased autophagy is detrimental, causing neuronal degeneration (Kamat et al. 2014; Jing and Lim 2012; Wong and Cuervo 2010; Liu et al. 2009). Autophagy can be divided into two broad categories, namely, microautophagy and macroautophagy. In microautophagy, the lysosome directly engulfs intracellular smaller molecules and is independent of nutritional deprivation (Filosto et al. 2011). On the other hand, in macroautophagy, autophagosome is formed with intracellular larger molecules. This is then fused with the lysosome to generate autophagolysosome and undergoes subsequent degradation. Macroautophagy of mitochondria is termed as mitophagy [74,75].
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].
Pathogenesis of Tuberculosis
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Divya B. Reddy, Jerrold J. Ellner
Autophagy is a homeostasis pathway wherein discrete portions of the cytoplasm are sequestered into an “autophagosome,” and delivered to lysosomes for degradation. Gutierrez and Singh have demonstrated that induction of autophagic pathways by drugs such as rapamycin can enhance host resistance to MTB by promoting phagosome maturation. In fact, IFN-γ-induced activation of p47 GTPases such as LRG-47 in MTB-infected macrophages leads to formation of large organelles with autophagolysosomal properties and in part, explains the reactive nitrogen- and oxygen-independent pathways of IFN-γ antimicrobial action.51 Similarly, Yuk et al. have shown that vitamin D3 exhibits antimycobacterial properties, by inducing autophagy in human monocytes via cathelicidin driven transcription of the autophagy-related genes Beclin-1 and Atg5.52 The role of autophagy in controlling bacterial burden and limiting tissue damaging inflammation is now becoming apparent and it is potentially a pathway for pharmacological manipulation.53
Cigarette smoke extract-induced inflammatory response via inhibition of the TFEB-mediated autophagy in NR8383 cells
Published in Experimental Lung Research, 2023
Shu-wen Xu, Yu-jie Zhang, Wen-mei Liu, Xin-fang Zhang, Yuan Wang, Shui-ying Xiang, Jing-chao Su, Zi-bing Liu
LC3 is a recognized autophagy specific marker. With the modification of autophagy-related protein 4 (ATG4), LC3-I gradually transforms into LC3-II, which is located on the membranes of autophagosomes. Therefore, the ratio of LC3II/I protein can reflect the number of autophagosomes.30 In our study, we found that in the CSE group, the number of autophagosomes and the ratio of LC3II/I protein markedly increased in NR8383 cells, whereas autophagy is a dynamic process including the following steps: initiation of autophagy, extension of autophagosome membrane, formation of autophagy-lysosome and degradation of lysosome.31 Therefore, the increasing number of autophagosomes may be related to the activation of autophagy, or the abnormal degradation of autolysosomes. Thus, we further investigated the expression of autophagy substrate protein P62, which is negatively correlated with autophagy. Our results indicated that the ratio of LC3II/I protein and the level of P62 protein significantly were increased in the CSE group. Combined with the increasing number of autophagosomes in the CSE group observed by TEM, we believed that CSE mainly affected the degradation stage of autophagy, resulting in the accumulation of impaired proteins and organelles.
Autophagy in peripheral blood mononuclear cells is associated with body fat percentage
Published in Archives of Physiology and Biochemistry, 2023
Fabiano T. Amorim, Roberto C. Nava, Kurt A. Escobar, Zidong Li, Anna M. Welch, Zachary J. Fennel, Zachary J. McKenna, Ann L. Gibson
Macroautophagy (herein referred to as autophagy) is a catabolic cellular maintenance system responsible for the identification, degradation, and recycling of dysfunctional and damaged proteins, organelles, and intracellular pathogens (Yorimitsu and Klionsky 2005). The autophagic process involves the formation of double membrane vesicles called autophagosomes. These structures sequester damaged organelles and mis-folded proteins and fuse with lysosomes forming autolysosomes in which the cargo is degraded. The constituent products are then released into the cytoplasm for use in cellular processes, including production of new proteins and metabolism. This proteostatic system is activated by nutrient restriction and energetic challenge (Vainshtein and Hood 2016). Autophagy prevents the accumulation of deleterious cytosolic components and is essential for the maintenance of cellular homeostasis (Feng et al.2014). Dysregulation of autophagy has been implicated in many diseases including cardiovascular disease, obesity, and type II diabetes (Murrow and Debnath 2013).
The potential interplay between opioid and the toll-like receptor 4 (TLR-4)
Published in Immunopharmacology and Immunotoxicology, 2023
Nasrin Zare, Marjan Pourhadi, Golnaz Vaseghi, Shaghayegh Haghjooy Javanmard
Streptococcus pneumonia induces IL-23 production by dendritic cells (DCs) via activation of TLR-2 and −4 signaling pathway. The high doses of morphine significantly down-regulate IL-23 production in a dose-dependent manner [73]. Autophagosome maturation and autophagolysosomal fusion are required for the efficient elimination of internalized pathogens and survival of pathogens within macrophages. It was shown that morphine increases the susceptibility to infection and the prevalence of persistent infection in the drug abuse population. The evaluation of the effect of morphine and LPS on TLR-4 expression in bone marrow-derived macrophages (BMDMs) reveals morphine mediates LPS-induced autophagy initiation via a TLR-4-dependent pathway and inhibits autophagolysosomal fusion through TLR-4 independent pathways [79].