Article
Pharmacology & Pharmacy
Angelica Jardim Costa, Adolfo Garcia Erustes, Rita Sinigaglia, Carlos Eduardo Neves Girardi, Gustavo Jose da Silva Pereira, Rodrigo Portes Ureshino, Soraya Soubhi Smaili
Summary: In young striatum, lithium increased tissue viability and decreased ROS generation, accompanied by enhanced expression of autophagy-related proteins. However, in aged striatum, lithium reduced autophagic flux and increased oxygen consumption rate. Ultrastructural changes in aged rats' striatum included electron-dense mitochondria with disarranged cristae after consuming lithium for 30 days.
Article
Cell Biology
Satoshi Minami, Shinsuke Sakai, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Hiroaki Yonishi, Jun Nakamura, Shihomi Maeda, Sho Matsui, Isao Matsui, Yoshitaka Isaka
Summary: Chronic kidney disease (CKD) has become an epidemic worldwide due to aging and increased obesity. The study reveals that autophagy deficiency induces the expression of FGF21, which plays a protective role against CKD progression by improving autophagy stagnation and maintaining mitochondrial homeostasis. This finding provides a potential novel treatment for CKD.
Review
Cell Biology
Manuela Morleo, Helena L. A. Vieira, Petra Pennekamp, Alessandro Palma, Liliana Bento-Lopes, Heymut Omran, Susana S. Lopes, Duarte C. Barral, Brunella Franco
Summary: Macroautophagy/autophagy is a self-degradative process that helps cells maintain energy balance. It has been found to have an interplay with cilia, microtubule-based organelles on mammalian cells. The selective autophagic degradation of ciliary proteins controls ciliogenesis, and cilia also control autophagy. The molecular mechanisms underlying this interaction are still not fully understood, and conflicting data exist. Understanding this axis is important for ciliopathies and autophagy-associated disorders.
Article
Cell Biology
Takeshi Yamamoto, Yoshitsugu Takabatake, Satoshi Minami, Shinsuke Sakai, Ryuta Fujimura, Atsushi Takahashi, Tomoko Namba-Hamano, Jun Matsuda, Tomonori Kimura, Isao Matsui, Jun-Ya Kaimori, Hiroaki Takeda, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Yoshitaka Isaka
Summary: The study found that supplementation with EPA can alleviate renal lipotoxicity by reducing phospholipid accumulation in lysosomes, improving mitochondrial dysfunction, reducing inflammation and fibrosis. EPA alleviates renal lipotoxicity by improving lysosomal function and autophagic flux in both high-fat diet-fed mice and isolated PTECs cultured in palmitic acid, indicating its potential as a novel treatment for obesity-related kidney diseases.
Review
Biochemistry & Molecular Biology
Michael Takla, Swati Keshri, David C. Rubinsztein
Summary: TFEB is a critical transcription factor involved in multiple physiological functions. Pathological states modify TFEB function by regulating its post-translational modifications, which can have both protective and deleterious effects on tissue survival. Understanding the post-translational modifications of TFEB is important for the development of diseases such as neurodegeneration and cancer.
Review
Cell Biology
Kihyoun Park, Myung-Shik Lee
Summary: Autophagy plays a crucial role in maintaining organelle function and intracellular nutrient balance. Dysregulated autophagy is implicated in various diseases, including metabolic disorders, neurodegenerative diseases, infections, and cardiovascular diseases. Research is underway to find autophagy modulators for the treatment of these diseases and it is expected that authentic autophagy modulators will be developed in the near future.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Makiko Mochizuki-Kashio, Hiroko Shiozaki, Toshio Suda, Ayako Nakamura-Ishizu
Summary: This review highlights the importance of metabolic regulation, including anaerobic metabolism, mitochondrial metabolism, and lysosomal regulation, in determining the cell fate of HSCs and maintaining hematopoietic homeostasis. These mechanisms are essential for the balance of hematopoietic system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Food Science & Technology
Xiaoxu Wang, Yu Song, Peixu Cong, Zhigao Wang, Yanjun Liu, Jie Xu, Changhu Xue
Summary: Docosahexaenoic acid-acylated astaxanthin monoester (AST-DHA) can rectify autophagic impairment in Alzheimer's disease and provide neuroprotection in Aβ-related pathology.
MOLECULAR NUTRITION & FOOD RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Hye Eun Lee, Min Kyo Jung, Seul Gi Noh, Hye Bin Choi, Se Hyun Chae, Jae Hyeok Lee, Ji Young Mun
Summary: Iron overload in the brain caused by a specific point mutation in the WD Repeat Domain 45 (WDR45) gene is associated with autophagy defects, altered organelle structures, and changes in the expression of genes related to lipid metabolism, mitochondrial function, and autophagy. The accumulation of iron primarily in lysosomal vesicles leads to impaired lipid metabolism, mitochondrial disorder, and unbalanced autophagy fluxes due to WDR45 deficiency.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Huan Wang, Yuting Shi, Dannv Ma, Mengqing Cao, Yuchao Sun, Xinyuan Jiang, Zhiyong Xu, Yongfang Wang, Ying Yang, Yueli Shi, Kai Wang
Summary: Currently, patients with lung cancer who have drug resistance or poor survival rates urgently require new therapeutic strategies. In this study, we found that Cinchonine can act as an autophagy suppressor and exert anti-tumor effects by inhibiting autophagy, elevating ROS levels, accumulating damaged mitochondria, and promoting apoptosis. Additionally, Cin upregulates PD-L1 expression in lung cancer cells, and the combination of Cin and PD-L1 blockade significantly reduces tumor growth.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Environmental Sciences
Qiuyi Zhao, Weizhe Pan, Jia Li, Shengnan Yu, Yan Liu, Xiaoli Zhang, Ruodi Qu, Qian Zhang, Ben Li, Xiaoyan Yan, Xuefeng Ren, Yulan Qiu
Summary: The combined exposure to arsenic and fluoride can cause severe pathological damage in brain tissue, impair spatial learning and memory ability, activate autophagy, disrupt synaptic structure and function, and induce neurotoxicity. There is an interaction between arsenic and fluoride, showing an antagonistic effect.
Review
Biochemistry & Molecular Biology
Jennifer J. Lee, Vaibhav Jain, Ravi K. Amaravadi
Summary: Despite advances in targeted therapy and immunotherapy, treating RAS mutant cancers remains challenging. These cancers have been found to activate adaptive resistance mechanisms like autophagy during MAPK inhibition. Recent focus has been on developing MAPK pathway and autophagy inhibitors for potential synthetic lethal approaches in cancer therapy, with ongoing clinical trials to evaluate their efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Cell Biology
Subhadip Mukhopadhyay, Joel Encarnacion-Rosado, Alec C. Kimmelman
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor survival rate and autophagy plays a role in its progression. Autophagy controls mitochondrial metabolism by regulating bioavailable iron in PDAC. Inhibition of autophagy in PDAC leads to mitochondrial dysfunction and cancer-associated fibroblasts (CAFs) provide iron to autophagy-inhibited tumor cells, increasing their resistance to autophagy inhibition. Combining a low iron diet with autophagy inhibition improves tumor response in PDAC models.
Article
Pharmacology & Pharmacy
Han Wang, Guiqian Fang, Huimin Chen, Maomao Hu, Yajuan Cui, Boyang Wang, Yudong Su, Yu Liu, Bo Dong, Xintian Shao
Summary: The study developed a new lysosome biosensor CNN for tracking lysosomes in living cells under both physiological and pathological conditions. High glucose conditions induced stress in lysosomes and altered the morphology of mitochondria.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rachel Curnock, Katy Yalci, Johan Palmfeldt, Marja Jaattela, Bin Liu, Bernadette Carroll
Summary: The accumulation of senescent cells is a driver of aging, and one characteristic of senescent cells is an increase in lysosomal content. However, little is known about the causes and consequences of lysosomal biogenesis in senescence.
Review
Biochemistry & Molecular Biology
Shanikumar Goyani, Milton Roy, Rajesh Singh
Summary: TRIM-NHL proteins possess unique RNA binding ability and E3 ligase activity, playing crucial roles in cellular processes and potential involvement in various pathological conditions.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Wen-Dai Bao, Pei Pang, Xiao-Ting Zhou, Fan Hu, Wan Xiong, Kai Chen, Jing Wang, Fudi Wang, Dong Xie, Ya-Zhuo Hu, Zhi-Tao Han, Hong-Hong Zhang, Wang-Xia Wang, Peter T. Nelson, Jian-Guo Chen, Youming Lu, Heng-Ye Man, Dan Liu, Ling-Qiang Zhu
Summary: Iron homeostasis disturbance and ferroptosis play critical roles in the pathogenesis and progression of Alzheimer's disease, and targeting these processes may provide promising therapeutic approaches for this disease.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Dhruv Gohel, Lakshmi Sripada, Paresh Prajapati, Fatema Currim, Milton Roy, Kritarth Singh, Anjali Shinde, Minal Mane, Darshan Kotadia, Flora Tassone, Nicolas Charlet-Berguerand, Rajesh Singh
Summary: This study analyzed the impact of CGG repeat expansion on mitochondrial miRNAs and cellular functions, highlighting the critical role of miR-320a in FXTAS pathology. Transfection of miR-320a mimic was found to restore mitochondrial functions and rescue cell death in cells expressing CGG permutation, indicating its potential therapeutic value in FXTAS.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Hitesh Vasiyani, Anjali Shinde, Milton Roy, Minal Mane, Kritarth Singh, Jyoti Singh, Dhruv Gohel, Fatema Currim, Khushali Vaidya, Mahesh Chhabria, Rajesh Singh
Summary: The study demonstrates that c-di-AMP can activate the type-1 IFN response in ER-negative breast cancer cells, which is correlated with STING expression. Furthermore, c-di-AMP induces mitochondrial-mediated cell death and inhibits clonogenicity of triple-negative breast cancer cells.
Article
Oncology
Anjali Shinde, Hyeryeon Jung, Hayun Lee, Kritarth Singh, Milton Roy, Dhruv Gohel, Han Byeol Kim, Minal Mane, Hitesh Vasiyani, Fatema Currim, Yu Ri Seo, Seojin Yang, Ara Cho, Eugene C. Yi, Rajesh Singh
Summary: The study shows that TNF-alpha can regulate the survival and proliferation of aggressive tumor cells by modulating the levels of critical assembly factors and subunits involved in mitochondrial respiratory chain supercomplexes organization and function, favoring the rewiring of mitochondrial metabolism towards anaplerosis to support the survival and proliferation of breast cancer cells. The results strongly suggest that TNF-alpha differentially regulates metabolic adaptation in ER/PR +ve (MCF-7) and ER/PR -ve (MDA-MB-231) cells by modulating the mitochondrial supercomplex assembly and activity.
CANCER & METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Milton Roy, Rajesh Singh
Summary: TRIMs, as RING domain-containing E3 ligases, are involved in regulating the NF-kappa B pathway and may lead to unique outcomes in different pathophysiological conditions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Endocrinology & Metabolism
Dana M. Niedowicz, Wang-Xia Wang, Doug A. Price, Peter T. Nelson
Summary: Thyroid hormone perturbation is common, affecting a significant portion of the elderly population. Previous research primarily focused on in utero and developmental effects, with less understanding of the impact on the adult brain. This study used pharmacological agents to simulate hyperthyroidism and hypothyroidism in middle-aged mice, revealing compensatory mechanisms in brain tissue through gene expression changes in response to TH fluctuation.
JOURNAL OF THYROID RESEARCH
(2021)
Article
Pathology
Jozsef Gal, Yuriko Katsumata, Haining Zhu, Sukanya Srinivasan, Jing Chen, Lance Allen Johnson, Wang-Xia Wang, Lesley Renee Golden, Donna M. Wilcock, Gregory A. Jicha, Matthew D. Cykowski, Peter Tobias Nelson
Summary: The proteomic analysis of human amygdala indicates that ApoE is not only a genetic risk factor but also an aberrantly aggregated protein, suggesting that ApoE may play an active disease-driving mechanistic role in individuals lacking the APOE epsilon 4 allele.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Cell Biology
Paresh Prajapati, Wang-Xia Wang, Steven A. Pesina, Urim Geleta, Joe E. Springer
Summary: Sex plays a significant role in neuroinflammatory responses to traumatic brain injury (TBI), and inflammatory microRNAs (miRNAs) may contribute to the sexually dimorphic neuroinflammatory response.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Cell Biology
Milton Roy, Kritarth Singh, Anjali Shinde, Jyoti Singh, Minal Mane, Sawani Bedekar, Yamini Tailor, Dhruv Gohel, Hitesh Vasiyani, Fatema Currim, Rajesh Singh
Summary: The study identified TRIM proteins as potential feedback regulators of the TNF-alpha-induced NF-kappa B pathway. TRIM15 was found to be a late response gene induced by TNF-alpha and inhibits the NF-kappa B pathway in human cell lines. It promotes turnover of K63-linked ubiquitin chains and inhibits the activity of TAK1 and TRIM8, thus regulating the proinflammatory NF-kappa B pathway.
CELLULAR SIGNALLING
(2022)
Review
Cell Biology
Shatakshi Shukla, Fatema Currim, Rajesh Singh
Summary: Exosomes play an important role in intercellular communication and maintaining cellular homeostasis during development and differentiation. Dysregulation in exosome-mediated communication can lead to developmental defects and chronic diseases. Exosomes are heterogeneous and can vary in size, membrane protein abundance, and cargo content. This review focuses on the latest developments in exosome biogenesis pathways, heterogeneity, selective cargo enrichment, and isolation techniques. Understanding the heterogeneity and selective cargo enrichment of extracellular vesicles may provide insights into disease severity and early prognosis, and specific subtypes of exosomes can be used as therapeutic tools and biomarkers for specific diseases.
BIOLOGY OF THE CELL
(2023)
Article
Biochemistry & Molecular Biology
Dhruv Gohel, Shatakshi Shukla, Wenson David Rajan, Bartosz Wojtas, Bozena Kaminska, Rajesh Singh
Summary: Stroke is a major cause of death and disabilities globally. Mitochondria play a critical role in inflammation and cell death, and mitochondrial dysfunction can lead to inflammatory responses. This study found that the pattern of miRNAs associated with mitochondrial functions changes under ischemic conditions, and the altered miRNAs target mitochondrial proteins involved in maintaining mitochondrial homeostasis.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
Gopal V. Velmurugan, W. Brad Hubbard, Paresh Prajapati, Hemendra J. Vekaria, Samir P. Patel, Alexander G. Rabchevsky, Patrick G. Sullivan
Summary: This study aimed to improve mitochondrial function after brain injury by targeting LDL receptor-related protein 1 (LRP1) and demonstrated it as a potential pharmacotherapeutic strategy. The results showed that oxidative stress increased mitochondrial quantity, while LRP1 deficiency significantly decreased mitochondrial fragmentation, preserving mitochondrial function and cell growth. Therefore, targeting LRP1 to improve mitochondrial function may be used for the treatment of traumatic brain injury and other neurodegenerative diseases.
Article
Cell Biology
Wang-Xia Wang, Paresh Prajapati, Hemendra J. Vekaria, Malinda Spry, Amber L. Cloud, Patrick G. Sullivan, Joe E. Springer
Summary: The study found that mitochondria-enriched miRNAs showed persistent alterations in injured hippocampal cells in rats after severe controlled cortical impact injury, while miRNAs not enriched in mitochondria did not exhibit significant changes in mitochondria. Nanoparticle delivery of miR-146a showed potential in modulating pro-inflammatory effectors in the injured brain.
NEURAL REGENERATION RESEARCH
(2021)