Mitochondria is an important drug target for ailments ranging from neoplastic to neurodegenerative diseases and metabolic diseases. Here, we describe the synthesis of chloroquine analogs and show the results of mitochondrial ATP inhibition testing. T...
The mitochondrial pyruvate carrier (MPC) is a transmembrane protein complex critical for cellular energy metabolism, enabling the transport of pyruvate from the cytosol into the mitochondria, where it fuels the citric acid cycle. By regulating this e...
Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA), a natural pyrone, is a potent chemosensitizing agent of...
(1) The cardio-reno-metabolic benefits of the SGLT2 inhibitors canagliflozin (cana), dapagliflozin (dapa), ertugliflozin (ertu), and empagliflozin (empa) have been demonstrated, but it remains unclear whether they exert different off-target effects i...
Chronic myeloid leukemia (CML) is a hematological malignancy that arises from the transformation of stem hematopoietic cells by the fusion oncogene BCR/ABL and subsequent clonal expansion of BCR/ABL-positive progenitor leukemic cells. The BCR/ABL pro...
Ten-eleven translocation 1 (TET1) is a methylcytosine dioxygenase involved in active DNA demethylation. In our previous study, we demonstrated that TET1 reprogrammed the ovarian cancer epigenome, increased stem properties, and activated various regul...
Mycothiazole, a polyketide metabolite isolated from the marine sponge Cacospongia mycofijiensis, is a potent inhibitor of metabolic activity and mitochondrial electron transport chain complex I in sensitive cells, but other cells are relatively insen...
Damage to cerebral mitochondria, particularly opening of mitochondrial permeability transition pore (MPTP), is a key mechanism of ischemic brain injury, therefore, modulation of MPTP may be a potential target for a neuroprotective strategy in ischemi...
Dysregulational EGFR, KRAS, and mTOR pathways cause metabolic reprogramming, leading to progression of gastric cancer. Afatinib (Afa) is a broad-spectrum tyrosine kinase inhibitor that reduces cancer growth by blocking the EGFR family. MicroRNA 125 (...
RhoA-regulated gene transcription by serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factors (MRTFs) signaling pathway has emerged as a promising therapeutic target for pharmacological intervention in mult...
Human cell-based assays for neurotoxicity (NT) and developmental neurotoxicity (DNT) have reached a high level of readiness, but some tests require improvements in the specificity and sensitivity at which mitochondrial toxicants are detected. This st...
Recent studies have indicated the critical importance of mitochondria in the induction and progression of ferroptosis. There is evidence indicating that tert-butyl hydroperoxide (TBH), a lipid-soluble organic peroxide, is capable of inducing ferropto...
The mitochondrial pyruvate carrier (MPC) is an inner-mitochondrial membrane protein complex that has emerged as a drug target for treating a variety of human conditions. A heterodimer of two proteins, MPC1 and MPC2, comprises the functional MPC compl...
Cancer cells may stimulate glycolytic flux when O2 becomes insufficient. Increase in L-lactate release therefore appears as an escape mechanism to drugs targeting mitochondrial respiration but also represents a response that may be exploited to scree...
Intracellular calcium homeostasis disorder and mitochondrial dysfunction are involved in many acute and chronic brain diseases, including ischemic brain injury. An imbalance in mitochondrial fission and fusion is one of the most important structural...
The mitochondrial Ca2+ uptake in trypanosomatids shares biochemical characteristics with that of animals. However, the composition of the mitochondrial Ca2+ uniporter complex (MCUC) in these parasites is quite peculiar, suggesting lineage-specific ad...
The aim of the study was to investigate the effect of inhibitors of mitochondrial respiratory chain complexes I, III, and IV on the electromechanical activity in human myocardium.
Material and methods. The experiments were performed on the human myoc...
The voltage-dependent anion channel (VDAC) is the primary regulating pathway of water-soluble metabolites and ions across the mitochondrial outer membrane. When reconstituted into lipid membranes, VDAC responds to sufficiently large transmembrane pot...
The multi-kinase inhibitor sorafenib is a primary treatment modality for advanced-stage hepatocellular carcinoma (HCC). However, the therapeutic benefits are short-lived due to innate and acquired resistance. Here, we examined how HCC cells respond t...
Mitochondria—critical metabolic hubs in eukaryotic cells—are involved in a wide range of cellular functions, including differentiation, proliferation, and death. Mitochondria import most of their proteins from the cytosol in a linear form...
Caseinolytic protease P (ClpP) is a mitochondrial serine protease. In mammalian cells, the heterodimerization of ClpP and its AAA+ ClpX chaperone results in a complex called ClpXP, which has a relevant role in protein homeostasis and in maintaining m...
Understanding the mechanisms underlying glucocorticoid (GC) resistance in B-cell acute lymphoblastic leukemia (B-ALL) is essential to improve survival rates in relapsed children. We previously showed that GCs paradoxically induced their own resistanc...
Background: The human mitochondrial ClpP is a serine protease located in the mitochondrial matrix responsible for degrading short lived regulatory proteins as well as misfolded or damaged proteins, thereby maintaining cellular homeostasis. Proteastas...
Mitochondrial calcium (Ca2+) uptake plays a key role in mitochondrial physiology and disease development. This process is regulated by the mitochondrial calcium uniporter (MCU) complex. DS16570511 is a membrane-permeable drug that inhibits mitochondr...
The protein p32 (C1QBP) is a multifunctional and multicompartmental homotrimer that is overexpressed in many cancer types, including colon cancer. High expression levels of C1QBP are negatively correlated with the survival of patients. Previously, we...
Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our gro...
Drug combination therapy is a key approach in cancer treatments, aiming to improve therapeutic efficacy and overcome drug resistance. Evaluation of intracellular response in cancer cells to drug treatment may disclose the underlying mechanism of drug...
Acute kidney injury (AKI), a critical syndrome characterized by a rapid decrease of kidney function, is a global health problem. Src family kinases (SFK) are proto-oncogenes that regulate diverse biological functions including mitochondrial function....
The ubiquitin proteasomal system and autophagic pathway are two main protein degradation systems in eukaryotic cells. Inhibition of the proteasomal system with proteasome inhibitors for cancer treatment can cause neurotoxic side effects. In this stud...
PARP inhibitors are a clinically validated class of anticancer therapeutics that exploit synthetic lethality to target homologous recombination-deficient tumors, such as those carrying BRCA1/2 mutations. Nevertheless, the rational design of mitochond...
Acute kidney injury (AKI) remains a major clinical challenge, with high morbidity and limited therapeutic options. In recent years, mitochondria have gained considerable attention as key regulators of the metabolic and immune responses during renal i...
While BCR::ABL1 tyrosine kinase inhibitors have transformed the treatment paradigm for chronic myeloid leukemia (CML), disease progression and treatment resistance due to BCR::ABL1-dependent and BCR::ABL1-independent mechanisms remain a therapeutic c...
Two-dimensional cell cultures are established models in research for studying and perturbing cell-type specific functions. However, many limitations apply to the cell growth in a monolayer using standard cell culture media. Although they have been us...
The purpose of this article is to highlight the role of dynamin-related protein 1 (Drp1) in abnormal mitochondrial dynamics, mitochondrial fragmentation, autophagy/mitophagy, and neuronal damage in Alzheimer’s disease (AD) and other neurological dise...
Neuroblastoma (NB) is the most prevalent paediatric extracranial solid tumour, which remains a major therapeutic challenge, especially in cases of recurrent and disseminated disease. c-Jun N-terminal kinases (JNKs) are increasingly evidenced to play...
Mitochondria are the powerhouses of cells, also involved in ROS (reactive oxygen species) generation and cellular death regulation. Thus, several diseases are associated with mitochondrial impairment, including cardiovascular disorders (CVDs). Since...
We examined the effects of the ferrocene-based histone deacetylase-3 inhibitor Pojamide (N1-(2-aminophenyl)-N8-ferrocenyloctanediamide) and its two derivatives N1-(2-aminophenyl)-N6-ferrocenyladipamide and N1-(2-aminophenyl)-N8-ferroceniumoctanediami...
Smoking has been associated, among other factors, with musculoskeletal disorders. Although there is no consensus about the effects of smoking on osteoarthritis (OA), the increase in TNF-alpha in smokers has been considered an important factor in OA i...
We examined the effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) combined with the vascular endothelial growth factor receptor-1/2 inhibitor (3Z)-5-hydroxy-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-...
Enhanced control of species of Cryptococcus, non-fermentative yeast pathogens, was achieved by chemosensitization through co-application of certain compounds with a conventional antimicrobial drug. The species of Cryptococcus tested showed higher sen...
Neurodegenerative diseases are associated with increased levels of nitric oxide (NO) mainly produced by microglial cells through inducible nitric oxide synthase (iNOS) whose expression is induced by inflammatory stimuli. NO can both exert cytotoxic f...
HIV mother-to-child transmission (MTCT) continues to pose a significant public health challenge, especially in regions with limited resources, although the worldwide distribution of antiretroviral therapy (ART) has drastically lowered the risk of ver...
Cancer treatment is greatly challenged by drug resistance, highlighting the need for novel drug discoveries. Here, we investigated novel organoarsenic compounds regarding their resistance-breaking and apoptosis-inducing properties in leukemia and lym...
Despite the availability of a wide range of preventive measures and comprehensive treatment options following infection, the development of acquired immunodeficiency syndrome (AIDS) remains a persistent challenge. Nucleoside reverse transcriptase inh...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving the progressive degeneration of upper and lower motor neurons. While oxidative stress, RNA-binding protein (RBP) pathology, mitochondrial dysfunction, and glial–neuro...
Multiple myeloma and its precursor plasma cell dyscrasias affect 3% of the elderly population in the US. Proteasome inhibitors are an essential part of several standard drug combinations used to treat this incurable cancer. These drugs interfere with...
CCG-1423 is a Rho A pathway inhibitor that has been reported to inhibit Rho/SRF-mediated transcriptional regulation. Serum response factor and its cofactors, which include ternary complex factors and myocardin-related transcription factors, regulate...
ND1 subunit possesses the majority of the inhibitor binding domain of the human mitochondrial respiratory complex I. This is an attractive target for the search for new inhibitors that seek mitochondrial dysfunction. It is known, from in vitro experi...
Background/Objectives: Cathepsins, lysosomal proteases crucial for neuronal proteostasis, mediate the clearance of misfolded and aggregated proteins. Their dysregulation is implicated in neurodegenerative and neuropsychiatric disorders such as Alzhei...
Background: Tariquidar (Tq) is an inhibitor of the multidrug resistance (MDR) proteins relevant to ATP-binding cassette transporters (ABC transporters), which suppresses the ATP-dependent efflux of a variety of hydrophilic and amphipathic compounds,...
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