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Exercise Training, Mitochondrial Adaptations, and Aging
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Nashwa Cheema, Matthew Triolo, David A. Hood
Targeting of mitochondria for breakdown occurs via several possible pathways, although only two have been investigated in muscle. The first, and simpler, method, is mediated by BCL2/adenovirus E1B 19kDA protein interacting 3 (BNIP3) (65, 134, 191, 194), a mitophagy receptor. This protein, when recruited to the outer mitochondrial membrane (OMM), interacts with autophagosome embedded proteins such as LC3 and GABARAP. Alternatively, a more intricate process begins with the OMM localization of PTEN-induced putative kinase (PINK1) (81, 92, 108, 113), a kinase that is normally imported into healthy mitochondria and degraded (81, 126). This active form of PINK1 recruits and phosphorylates the E3-ubiquitin ligase Parkin (92, 108, 113, 156), which poly-ubiquitinates OMM proteins (148). These poly-ubiquitin chains bind to adapter proteins such as SQSTM1 (also referred to as p62) (53) or optineurin (181), which act as a tethering point between the mitochondrion and the autophagosome through binding with the embedded LC3-II or GABARAP. Both processes ultimately lead to organelle degradation.
Ascorbate and the Hypoxic Response in Cancer
Published in Qi Chen, Margreet C.M. Vissers, Cancer and Vitamin C, 2020
Christina Wohlrab, Caroline Kuiper, Gabi U. Dachs
HIF-regulated target genes are intimately involved in response to therapy. For example, HIF-1-dependent BNIP3 upregulation is responsible for hypoxia-induced resistance to etoposide treatment in vitro, via mitochondrial enlargement conferring protection against apoptosis [40]. Other mechanisms by which HIF-1 mediates hypoxia-induced chemoresistance include drug efflux, inhibition of cell senescence, inhibition of DNA damage, and decreased mitochondrial activity [41–44]. HIF-1 is also able to inhibit the oncogene MYC, resulting in cell cycle arrest and inhibition of DNA repair genes, which in turn will enhance response to chemotherapy [45], thus highlighting the complexity of the HIF-1 response.
Mitochondrial Dysfunction in Breast Cancer
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Thalita Basso Scandolara, Letícia Madureira Pacholak, Thayse Fachin Cormanique, Rodrigo Kern, Carolina Panis
Several pathways have been identified to be involved in mitophagy, such an example is BNIP3 gene with tumor suppression properties and that’s known to be induced by hypoxia, FOXO3, NFKB, TP53 and others tumor-related transcription factors (Chourasia and Macleod 2015; Chourasia et al. 2015; Qiao et al. 2016). Loss of BNIP3-dependent mitophagy has been shown to predict increased ROS production and progression to metastasis due to augmented expression of Hypoxia-inducible factor 1α (HIF-1α) (Chourasia and Macleod 2015; Chourasia et al. 2015). This fact is also associated with glycolysis and angiogenesis, specially in the triple-negative subtype when compared to other subtypes of breast cancer (Chourasia and Macleod 2015). Furthermore, in mouse models, loss of BNIP3 showed an increased in mitochondrial mass and a function reduction of mitochondria both in vivo and in vitro (Chourasia et al. 2015).
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
BNIP3 is a pro-apoptotic protein that enhances mitochondrial autophagy by inhibiting the fusion of damaged mitochondria to eliminate the damaged mitochondria [154]. In malignant glioma cells, ceramide, a simple sphingolipid with unique biophysical properties, could increase the expression of BNIP3, which further activated mitophagy and led to cancer cell death. Similarly, ethyl 3,4-dihydroxy benzoate, a compound that effectively inhibits tumour cell proliferation, could activate mitophagy as a result of the high expression of BNIP3 in oesophageal cancer cells, resulting in cancer cell death [155]. Ursolic and oleanolic induces mitophagy in human lung cancer cell line A549 through a PINK-dependent molecular pathway, which leads to the decrease of mitochondrial membrane potential and cell death [156]. Activating mitophagy can prevent the occurrence of tumours and partially promote the death of cancer cells. Therefore, the development of mitophagy activators and their therapeutic application in cancer is a future research direction.
Comparative Expression Analysis of Stress-Inducible Genes in Murine Immune Cells
Published in Immunological Investigations, 2020
Madoka Koyanagi, Yutaka Arimura
Bnip3 expression increased in Dex-administered mice and in chronically stressed BALB/c mice (Figures 1 and 4b). Although there has been no report on the role of BNIP3 in immune cells, BNIP3 is a Bcl-2 family protein with a BH3 domain and has been suggested to play a cell death-promoting function on mitochondria (Yasuda et al. 1998). Thus, it is possible that Bnip3 expression may be involved in the decrease of spleen cell after 5 days of stress. However, as Bnip3 induction did not occur after stress in the thymus, it is not posited to be involved in the apoptosis of DP cells in the thymus; however, other Bcl-2 family members may be involved in cell-loss mechanisms after stress. Accordingly, there may be different cell death pathways in peripheral T cells and thymocytes. Furthermore, it could be speculated that as TRP53INP1 and BNIP3 potentially have a role in killing immune cells, they might eventually suppress possible autoimmune disease elicited under severely stressful situations (Paunkovic et al. 1998).
Effect of titanium dioxide nanoparticles on DNA methylation in multiple human cell lines
Published in Nanotoxicology, 2020
Marta Pogribna, Nathan A. Koonce, Ammu Mathew, Beverly Word, Anil K. Patri, Beverly Lyn-Cook, George Hammons
GDF-15 is a member of the transforming growth factor-superfamily (Zhou et al. 2013). GDF-15 plays a role in the regulation of cellular responses to stress signals and inflammation, and tissue repair after acute injuries. The dysregulation of GDF-15 expression and signaling pathways is associated with diverse human diseases and cancer progression. GDF-15 methylation has been suggested to be involved in several cancers, including bladder cancer (Tsui et al. 2015), urothelial cancer (Monteiro-Reis et al. 2014), and glioblastoma (Kadowaki et al. 2012). BNIP3 has various cellular functions and has also been shown to be involved in various disease conditions, including myocardial ischemia, autophagy, and apoptosis, thereby, associated with the pathogenesis of diseases such as cardio-vascular disease and cancer (Chinnadurai et al. 2008). In several cancers, including liver (Calvisi et al. 2007), colorectal (Shimizu et al. 2010), pancreatic (Okami et al. 2004), and hematopoietic tumors (Murai et al. 2005), BNIP3 methylation has been observed.