• MinireviewNovember 30, 2023

    0 410 176

    Abstract : Autophagy dysfunction is associated with human diseases and conditions including neurodegenerative diseases, metabolic issues, and chronic infections. Additionally, the decline in autophagic activity contributes to tissue and organ dysfunction and aging-related diseases. Several factors, such as down-regulation of autophagy components and activators, oxidative damage, microinflammation, and impaired autophagy flux, are linked to autophagy decline. An autophagy flux impairment (AFI) has been implicated in neurological disorders and in certain other pathological conditions. Here, to enhance our understanding of AFI, we conducted a comprehensive literature review of findings derived from two well-studied cellular stress models: glucose deprivation and replicative senescence. Glucose deprivation is a condition in which cells heavily rely on oxidative phosphorylation for ATP generation. Autophagy is activated, but its flux is hindered at the autolysis step, primarily due to an impairment of lysosomal acidity. Cells undergoing replicative senescence also experience AFI, which is also known to be caused by lysosomal acidity failure. Both glucose deprivation and replicative senescence elevate levels of reactive oxygen species (ROS), affecting lysosomal acidification. Mitochondrial alterations play a crucial role in elevating ROS generation and reducing lysosomal acidity, highlighting their association with autophagy dysfunction and disease conditions. This paper delves into the underlying molecular and cellular pathways of AFI in glucose-deprived cells, providing insights into potential strategies for managing AFI that is driven by lysosomal acidity failure. Furthermore, the investigation on the roles of mitochondrial dysfunction sheds light on the potential effectiveness of modulating mitochondrial function to overcome AFI, offering new possibilities for therapeutic interventions.

  • MinireviewNovember 30, 2023

    0 276 102

    The Role of mRNA Quality Control in the Aging of Caenorhabditis elegans

    Hyunwoo C. Kwon , Yunkyu Bae , and Seung-Jae V. Lee

    Mol. Cells 2023; 46(11): 664-671

    Abstract : The proper maintenance of mRNA quality that is regulated by diverse surveillance pathways is essential for cellular homeostasis and is highly conserved among eukaryotes. Here, we review findings regarding the role of mRNA quality control in the aging and longevity of Caenorhabditis elegans, an outstanding model for aging research. We discuss the recently discovered functions of the proper regulation of nonsense-mediated mRNA decay, ribosome-associated quality control, and mRNA splicing in the aging of C. elegans. We describe how mRNA quality control contributes to longevity conferred by various regimens, including inhibition of insulin/insulin-like growth factor 1 (IGF-1) signaling, dietary restriction, and reduced mechanistic target of rapamycin signaling. This review provides valuable information regarding the relationship between the mRNA quality control and aging in C. elegans, which may lead to insights into healthy longevity in complex organisms, including humans.

  • MinireviewOctober 31, 2023

    0 681 253

    Abstract : The mammalian skin contains hair follicles, which are epidermal appendages that undergo periodic cycles and exhibit mini-organ features, such as discrete stem cell compartments and different cellular components. Wound-induced hair follicle neogenesis (WIHN) is the remarkable ability to regenerate hair follicles after large-scale wounding and occurs in several adult mammals. WIHN is comparable to embryonic hair follicle development in its processes. Researchers are beginning to identify the stem cells that, in response to wounding, develop into neogenic hair follicles, as well as to understand the functions of immune cells, mesenchymal cells, and several signaling pathways that are essential for this process. WIHN represents a promising therapeutic approach to the reprogramming of cellular states for promoting hair follicle regeneration and preventing scar formation. In the scope of this review, we investigate the contribution of several cell types and molecular mechanisms to WIHN.

  • MinireviewOctober 31, 2023

    0 496 167

    Sarcoma Immunotherapy: Confronting Present Hurdles and Unveiling Upcoming Opportunities

    Sehan Jeong , Sharmin Afroz , Donghyun Kang , Jeonghwan Noh , Jooyeon Suh , June Hyuk Kim , Hye Jin You , Hyun Guy Kang , Yi-Jun Kim , and Jin-Hong Kim

    Mol. Cells 2023; 46(10): 579-588

    Abstract : Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.

  • MinireviewSeptember 30, 2023

    0 591 247

    Updates on the Immune Cell Basis of Hepatic Ischemia-Reperfusion Injury

    Mi Jeong Heo , Ji Ho Suh , Kyle L. Poulsen , Cynthia Ju , and Kang Ho Kim

    Mol. Cells 2023; 46(9): 527-534

    Abstract : Liver ischemia-reperfusion injury (IRI) is the main cause of organ dysfunction and failure after liver surgeries including organ transplantation. The mechanism of liver IRI is complex and numerous signals are involved but cellular metabolic disturbances, oxidative stress, and inflammation are considered the major contributors to liver IRI. In addition, the activation of inflammatory signals exacerbates liver IRI by recruiting macrophages, dendritic cells, and neutrophils, and activating NK cells, NKT cells, and cytotoxic T cells. Technological advances enable us to understand the role of specific immune cells during liver IRI. Accordingly, therapeutic strategies to prevent or treat liver IRI have been proposed but no definitive and effective therapies exist yet. This review summarizes the current update on the immune cell functions and discusses therapeutic potentials in liver IRI. A better understanding of this complex and highly dynamic process may allow for the development of innovative therapeutic approaches and optimize patient outcomes.

  • MinireviewAugust 31, 2023

    0 798 206

    Abstract : The tail of the striatum (TS) is located at the caudal end in the striatum. Recent studies have advanced our knowledge of the anatomy and function of the TS but also raised questions about the differences between rodent and primate TS. In this review, we compare the anatomy and function of the TS in rodent and primate brains. The primate TS is expanded more caudally during brain development in comparison with the rodent TS. Additionally, five sensory inputs from the cortex and thalamus converge in the rodent TS, but this convergence is not observed in the primate TS. The primate TS, including the caudate tail and putamen tail, primarily receives inputs from the visual areas, implying a specialized function in processing visual inputs for action generation. This anatomical difference leads to further discussion of cellular circuit models to comprehend how the primate brain processes a wider range of complex visual stimuli to produce habitual behavior as compared with the rodent brain. Examining these differences and considering possible neural models may provide better understanding of the anatomy and function of the primate TS.

  • MinireviewJuly 31, 2023

    1 1268 341

    The Pleiotropic Face of CREB Family Transcription Factors

    Md. Arifur Rahman Chowdhury , Jungeun An , and Sangyun Jeong

    Mol. Cells 2023; 46(7): 399-413

    Abstract : cAMP responsive element-binding protein (CREB) is one of the most intensively studied phosphorylation-dependent transcription factors that provide evolutionarily conserved mechanisms of differential gene expression in vertebrates and invertebrates. Many cellular protein kinases that function downstream of distinct cell surface receptors are responsible for the activation of CREB. Upon functional dimerization of the activated CREB to cis-acting cAMP responsive elements within the promoters of target genes, it facilitates signal-dependent gene expression. From the discovery of CREB, which is ubiquitously expressed, it has been proven to be involved in a variety of cellular processes that include cell proliferation, adaptation, survival, differentiation, and physiology, through the control of target gene expression. In this review, we highlight the essential roles of CREB proteins in the nervous system, the immune system, cancer development, hepatic physiology, and cardiovascular function and further discuss a wide range of CREB-associated diseases and molecular mechanisms underlying the pathogenesis of these diseases.

  • MinireviewJune 30, 2023

    1 1200 300

    How Extracellular Reactive Oxygen Species Reach Their Intracellular Targets in Plants

    Jinsu Lee , Minsoo Han , Yesol Shin , Jung-Min Lee , Geon Heo , and Yuree Lee

    Mol. Cells 2023; 46(6): 329-336

    Abstract : Reactive oxygen species (ROS) serve as secondary messengers that regulate various developmental and signal transduction processes, with ROS primarily generated by NADPH OXIDASEs (referred to as RESPIRATORY BURST OXIDASE HOMOLOGs [RBOHs] in plants). However, the types and locations of ROS produced by RBOHs are different from those expected to mediate intracellular signaling. RBOHs produce O2•− rather than H2O2 which is relatively long-lived and able to diffuse through membranes, and this production occurs outside the cell instead of in the cytoplasm, where signaling cascades occur. A widely accepted model explaining this discrepancy proposes that RBOH-produced extracellular O2•− is converted to H2O2 by superoxide dismutase and then imported by aquaporins to reach its cytoplasmic targets. However, this model does not explain how the specificity of ROS targeting is ensured while minimizing unnecessary damage during the bulk translocation of extracellular ROS (eROS). An increasing number of studies have provided clues about eROS action mechanisms, revealing various mechanisms for eROS perception in the apoplast, crosstalk between eROS and reactive nitrogen species, and the contribution of intracellular organelles to cytoplasmic ROS bursts. In this review, we summarize these recent advances, highlight the mechanisms underlying eROS action, and provide an overview of the routes by which eROS-induced changes reach the intracellular space.

  • MinireviewJune 30, 2023

    0 942 293

    Structure-Based Insight on the Mechanism of N-Glycosylation Inhibition by Tunicamycin

    Danbi Yoon , Ju Heun Moon , Anna Cho , Hyejoon Boo , Jeong Seok Cha *, Yoonji Lee *, and Jiho Yoo *

    Mol. Cells 2023; 46(6): 337-344

    Abstract : N-glycosylation, a common post-translational modification, is widely acknowledged to have a significant effect on protein stability and folding. N-glycosylation is a complex process that occurs in the endoplasmic reticulum (ER) and requires the participation of multiple enzymes. GlcNAc-1-P-transferase (GPT) is essential for initiating N-glycosylation in the ER. Tunicamycin is a natural product that inhibits N-glycosylation and produces ER stress, and thus it is utilized in research. The molecular mechanism by which GPT triggers N-glycosylation is discussed in this review based on the GPT structure. Based on the structure of the GPT-tunicamycin complex, we also discuss how tunicamycin reduces GPT activity, which prevents N-glycosylation. This review will be highly useful for understanding the role of GPT in the N-glycosylation of proteins, as well as presents a potential for considering tunicamycin as an antibiotic treatment.

  • MinireviewMay 31, 2023

    2 1818 752

    The Role of Pyruvate Metabolism in Mitochondrial Quality Control and Inflammation

    Min-Ji Kim , Hoyul Lee , Dipanjan Chanda , Themis Thoudam , Hyeon-Ji Kang , Robert A. Harris , and In-Kyu Lee

    Mol. Cells 2023; 46(5): 259-267

    Abstract : Pyruvate metabolism, a key pathway in glycolysis and oxidative phosphorylation, is crucial for energy homeostasis and mitochondrial quality control (MQC), including fusion/fission dynamics and mitophagy. Alterations in pyruvate flux and MQC are associated with reactive oxygen species accumulation and Ca2+ flux into the mitochondria, which can induce mitochondrial ultrastructural changes, mitochondrial dysfunction and metabolic dysregulation. Perturbations in MQC are emerging as a central mechanism for the pathogenesis of various metabolic diseases, such as neurodegenerative diseases, diabetes and insulin resistance-related diseases. Mitochondrial Ca2+ regulates the pyruvate dehydrogenase complex (PDC), which is central to pyruvate metabolism, by promoting its dephosphorylation. Increase of pyruvate dehydrogenase kinase (PDK) is associated with perturbation of mitochondria-associated membranes (MAMs) function and Ca2+ flux. Pyruvate metabolism also plays an important role in immune cell activation and function, dysregulation of which also leads to insulin resistance and inflammatory disease. Pyruvate metabolism affects macrophage polarization, mitochondrial dynamics and MAM formation, which are critical in determining macrophage function and immune response. MAMs and MQCs have also been intensively studied in macrophage and T cell immunity. Metabolic reprogramming connected with pyruvate metabolism, mitochondrial dynamics and MAM formation are important to macrophages polarization (M1/M2) and function. T cell differentiation is also directly linked to pyruvate metabolism, with inhibition of pyruvate oxidation by PDKs promoting proinflammatory T cell polarization. This article provides a brief review on the emerging role of pyruvate metabolism in MQC and MAM function, and how dysfunction in these processes leads to metabolic and inflammatory diseases.

  • MinireviewMay 31, 2023

    1 1061 262

    Abstract : Obesity is a significant global health risk that can cause a range of serious metabolic problems, such as type 2 diabetes and cardiovascular diseases. Adipose tissue plays a pivotal role in regulating energy and lipid storage. New research has underlined the crucial role of splicing factors in the physiological and functional regulation of adipose tissue. By generating multiple transcripts from a single gene, alternative splicing allows for a greater diversity of the proteome and transcriptome, which subsequently influence adipocyte development and metabolism. In this review, we provide an outlook on the part of splicing factors in adipogenesis and thermogenesis, and investigate how the different spliced isoforms can affect the development and function of adipose tissue.

  • MinireviewApril 30, 2023

    1 1608 538

    Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases

    Won Kyu Kim , Wooseon Choi , Barsha Deshar , Shinwon Kang , and Jiyoon Kim

    Mol. Cells 2023; 46(4): 191-199

    Abstract : The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the ‘Golgi stress response,’ which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

Mol. Cells
Nov 30, 2023 Vol.46 No.11, pp. 655~725
Kim et al. (pp. 710-724) demonstrated that a pathogen-derived Ralstonia pseudosolanacearum type III effector RipL delays flowering time and enhances susceptibility to bacterial infection in Arabidopsis thaliana. Shown is the RipL-expressing Arabidopsis plant, which displays general dampening of the transcriptional program during pathogen infection, grown in long-day conditions.

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