Membrane-bound organelles and membraneless organelles (MLOs) coordinate various biological processes within eukaryotic cells. Among these, stress granules (SGs) are significant cytoplasmic MLOs that form in response to cellular stress, exhibiting liquid-like properties alongside stable substructures. SGs interact with diverse organelles, thereby influencing cellular pathways that are critical in both health and disease contexts. This review discusses the interplay between SGs and organelles and explores the methodologies employed to analyze interactions between SGs and other MLOs. Furthermore, it highlights the pivotal roles SGs play in regulating cellular responses and the pathogenesis of amyotrophic lateral sclerosis. Gaining insights into these interactions is essential for deciphering the mechanisms underlying both physiological processes and pathological conditions.
Humans ; Stress Granules/pathology* ; Organelles/metabolism* ; Amyotrophic Lateral Sclerosis/pathology* ; Animals ; Stress, Physiological ; Cytoplasmic Granules/metabolism*

During mitosis, the allocation of genetic material concurs with organelle transformation and distribution. The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression, cell fate determination, and organismal homeostasis. Small GTPases belonging to the Ras superfamily regulate various cell organelles during division. Being the key regulators of membrane dynamics, the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases, such as cancer and Alzheimer's disease. Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation. This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.
Humans ; Mitosis ; Monomeric GTP-Binding Proteins ; Neoplasms ; Organelles/physiology* ; Signal Transduction

Despite considerable efforts to prevent and treat cardiovascular disease (CVD), it has become the leading cause of death worldwide. Cardiac mitochondria are crucial cell organelles responsible for creating energy-rich ATP and mitochondrial dysfunction is the root cause for developing heart failure. Therefore, maintenance of mitochondrial quality control (MQC) is an essential process for cardiovascular homeostasis and cardiac health. In this review, we describe the major mechanisms of MQC system, such as mitochondrial unfolded protein response and mitophagy. Moreover, we describe the results of MQC failure in cardiac mitochondria. Furthermore, we discuss the prospects of 2 drug candidates, urolithin A and spermidine, for restoring mitochondrial homeostasis to treat CVD.
Adenosine Triphosphate ; Cardiovascular Diseases ; Cause of Death ; Heart Failure ; Heart ; Homeostasis ; Mitochondria ; Mitochondrial Degradation ; Organelles ; Quality Control ; Spermidine ; Unfolded Protein Response

Actin Cytoskeleton ; Axoneme ; Cytoskeleton ; Humans ; Infertility, Male ; Kartagener Syndrome ; Male ; Male ; Microtubule-Associated Proteins ; Microtubules ; Organelles ; Sperm Head ; Sperm Motility ; Spermatogenesis ; Spermatozoa ; Tail

Autophagy is a homeostatic mechanism that discards not only invading pathogens but also damaged organelles and denatured proteins via lysosomal degradation. Increasing evidence suggests a role for autophagy in inflammatory diseases, including infectious diseases, Crohn's disease, cystic fibrosis, and pulmonary hypertension. These studies suggest that modulating autophagy could be a novel therapeutic option for inflammatory diseases. Eosinophils are a major type of inflammatory cell that aggravates airway inflammatory diseases, particularly corticosteroid-resistant inflammation. The eosinophil count is a useful tool for assessing which patients may benefit from inhaled corticosteroid therapy. Recent studies demonstrate that autophagy plays a role in eosinophilic airway inflammatory diseases by promoting airway remodeling and loss of function. Genetic variant in the autophagy gene ATG5 is associated with asthma pathogenesis, and autophagy regulates apoptotic pathways in epithelial cells in individuals with chronic obstructive pulmonary disease. Moreover, autophagy dysfunction leads to severe inflammation, especially eosinophilic inflammation, in chronic rhinosinusitis. However, the mechanism underlying autophagy-mediated regulation of eosinophilic airway inflammation remains unclear. The aim of this review is to provide a general overview of the role of autophagy in eosinophilic airway inflammation. We also suggest that autophagy may be a new therapeutic target for airway inflammation, including that mediated by eosinophils.
Airway Remodeling ; Asthma ; Autophagy ; Communicable Diseases ; Crohn Disease ; Cystic Fibrosis ; Eosinophils ; Epithelial Cells ; Humans ; Hypertension, Pulmonary ; Inflammation ; Organelles ; Pulmonary Disease, Chronic Obstructive

Macroautophagy/autophagy is a conserved degradation system that engulfs intracytoplasmic contents, including aggregated proteins and organelles, which is crucial for cellular homeostasis. During aging, cellular factors suggested as the cause of aging have been reported to be associated with progressively compromised autophagy. Dysfunctional autophagy may contribute to age-related diseases, such as neurodegenerative disease, cancer, and metabolic syndrome, in the elderly. Therefore, restoration of impaired autophagy to normal may help to prevent age-related disease and extend lifespan and longevity. Therefore, this review aims to provide an overview of the mechanisms of autophagy underlying cellular aging and the consequent disease. Understanding the mechanisms of autophagy may provide potential information to aid therapeutic interventions in age-related diseases.
Aged ; Aging ; Autophagy ; Cell Aging ; DNA Damage ; Homeostasis ; Humans ; Longevity ; Neurodegenerative Diseases ; Organelles ; Oxidative Stress ; Telomere Shortening

BACKGROUND: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys. METHODS: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy. RESULTS: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells. CONCLUSION: The activation of nuclear factor E2-related factor 2 (Nrf2)–HO–1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.
Apoptosis ; Autophagy ; Caspase 3 ; Diabetic Nephropathies ; Down-Regulation ; Glucose ; Heme Oxygenase-1 ; Homeostasis ; Humans ; Kidney ; Lysosomes ; NF-E2-Related Factor 2 ; Organelles ; Oxidative Stress ; Reactive Oxygen Species

Particulate matter (PM), which refers to the mixture of particles present in the air, can have harmful effects. Damage to cells by PM, including disruption of organelles and proteins, can trigger autophagy, and the relationship between autophagy and PM has been well studied. However, the cellular regulators of PM-induced autophagy have not been well characterized, especially in keratinocytes. The Aryl Hydrocarbon Receptor (AhR) is expressed in the epidermis and is activated by PM. In this study, we investigated the role of the AhR in PM-induced autophagy in HaCaT cells. Our results showed that PM led to AhR activation in keratinocytes. Activation of the AhR-target gene CYP1A1 by PM was reduced by co-treatment with α-naphthoflavone (α-NF), an AhR inhibitor. We also evaluated activation of the autophagy pathway in PM-treated keratinocytes. In HaCaT cells, treatment with PM treatment led to the induction of microtubules-associated proteins light chain 3 (LC3) and p62/SQSTM1, which are essential components of the autophagy pathway. To study the role of the AhR in mediating PM-induced autophagy, we treated cells with α-NF or used an siRNA against AhR. Expression of LC3-ІІ induced by PM was decreased in a dose dependent manner by α-NF. Furthermore, knockdown of AhR with siAhR diminished PM-induced expression of LC3-ІІ and p62. Together, these results suggest that inhibition of the AhR decreases PM-induced autophagy. We confirmed these results using the autophagy-inhibitors BAF and 3-MA. Taken together, our results indicate that exposure to PM induces autophagy via the AhR in HaCaT keratinocytes.
Autophagy ; Cytochrome P-450 CYP1A1 ; Epidermis ; Keratinocytes ; Negotiating ; Organelles ; Particulate Matter ; Receptors, Aryl Hydrocarbon ; RNA, Small Interfering

The dynamics of the actin cytoskeleton plays a pivotal role in the process of cell division, the transportation of organelles, vesicle trafficking and cell movement. Human immunodeficiency virus type 1 (HIV-1) hijacks the actin dynamics network during the viral entry and migration of the pre-integration complex (PIC) into the nucleus. Actin dynamics linked to HIV-1 has emerged as a potent therapeutic target against HIV infection. Although some inhibitors have been intensely analyzed with regard to HIV-1 infection, their effects are sometimes disputed and the exact mechanisms for actin dynamics in HIV infection have not been well elucidated. In this study, the small molecules regulating HIV-1 infection from diverse inhibitors of the actin dynamic network were screened. Two compounds, including Chaetoglobosin A and CK-548, were observed to specifically bar the viral infection, while the cytochalasin family, 187-1, N-WASP inhibitor, Rho GTPase family inhibitors (EHop-016, CID44216842, and ML-141) and LIMK inhibitor (LIM domain kinase inhibitor) increased the viral infection without cytotoxicity within a range of ~ µM. However, previously known inhibitory compounds of HIV-1 infection, such as Latrunculin A, Jasplakinolide, Wiskostatin and Swinholide A, exhibited either an inhibitory effect on HIV-1 infection combined with severe cytotoxicity or showed no effects. Our data indicate that Chaetoglobosin A and CK-548 have considerable potential for development as new therapeutic drugs for the treatment of HIV infection. In addition, the newly identified roles of Cytochalasins and some inhibitors of Rho GTPase and LIMK may provide fundamental knowledge for understanding the complicated actin dynamic pathway when infected by HIV-1. Remarkably, the newly defined action modes of the inhibitors may be helpful in developing potent anti-HIV drugs that target the actin network, which are required for HIV infection.
Actin Cytoskeleton ; Actins ; Anti-HIV Agents ; Cell Division ; Cell Movement ; Cytochalasins ; GTP Phosphohydrolases ; HIV Infections ; HIV-1 ; Humans ; Organelles ; Phosphotransferases ; Transportation

Stress severely disturbs physiological and mental homeostasis which includes adult neurogenesis in hippocampus. Neurogenesis in hippocampus is a key feature to adapt to environmental changes and highly regulated by multiple cellular signaling pathways. The primary cilium is a cellular organelle, which acts as a signaling center during development and neurogenesis in adult mice. However, it is not clear how the primary cilia are involved in the process of restraint (RST) stress response. Using a mouse model, we examined the role of primary cilia in repeated and acute RST stress response. Interestingly, RST stress increased the number of ciliated cells in the adult hippocampal dentate gyrus (DG). In our RST model, cell proliferation in the DG also increased in a time-dependent manner. Moreover, the analysis of ciliated cells in the hippocampal DG with cell type markers indicated that cells that were ciliated in response to acute RST stress are neurons. Taken together, these findings suggest that RST stress response is closely associated with an increase in the number of ciliated neurons and leads to an increase in cell proliferation.
Adult ; Animals ; Cell Proliferation ; Cilia ; Dentate Gyrus ; Hippocampus ; Homeostasis ; Humans ; Mice* ; Neurogenesis ; Neurons* ; Organelles