Mitochondrial dysfunction

Unhealthy sources of fats, ultra-processed foods with added sugars, and a sedentary lifestyle make humans more susceptible to developing overweight and obesity. While lipids constitute an integral component of the organism, excessive and abnormal lipid accumulation that exceeds the storage capacity of lipid droplets disrupts the intracellular composition of fatty acids and results in the release of deleterious lipid species, thereby giving rise to a pathological state termed lipotoxicity. This condition induces endoplasmic reticulum stress, mitochondrial dysfunction, inflammatory responses, and cell death...

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PURPOSE: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function. METHODS: An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109  CFU daily...

Several metabolic pathways are essential for the physiological regulation of immune cells, but their dysregulation can cause immune dysfunction. Hypermetabolic and hypometabolic states represent deviations in the magnitude and flexibility of effector cells in different contexts, for example in autoimmunity, infections or cancer. To study immunometabolism, most methods focus on bulk populations and rely on in vitro activation assays. Nowadays, thanks to the development of single-cell technologies, including multiparameter flow cytometry, mass cytometry, RNA cytometry, among others, the metabolic state of individual immune cells can be measured in a variety of samples obtained in basic, translational and clinical studies...

Stroke, the leading cause of disability and cognitive impairment, is also the second leading cause of death worldwide. The drugs with multi-targeted brain cytoprotective effects are increasingly being advocated for the treatment of stroke. Irisin, a newly discovered myokine produced by cleavage of fibronectin type III domain 5, has been shown to regulate glucose metabolism, mitochondrial energy, and fat browning. A large amount of evidence indicated that irisin could exert anti-inflammatory, anti-apoptotic, and antioxidant properties in a variety of diseases such as myocardial infarction, inflammatory bowel disease, lung injury, and kidney or liver disease...

Idiopathic Parkinson's disease (PD) is epidemiologically linked with exposure to toxicants such as pesticides and solvents, which comprise a wide array of chemicals that pollute our environment. While most are structurally distinct, a common cellular target for their toxicity is mitochondrial dysfunction, a key pathological trigger involved in the selective vulnerability of dopaminergic neurons. We and others have shown that environmental mitochondrial toxicants such as the pesticides rotenone and paraquat, and the organic solvent trichloroethylene (TCE) appear to be influenced by the protein LRRK2, a genetic risk factor for PD...

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction...

Airborne fine particulate matter (PM2.5 ) exposure is closely associated with metabolic disturbance, in which brown adipose tissue (BAT) is one of the main contributing organs. However, knowledge of the phenotype and mechanism of PM2.5 exposure-impaired BAT is quite limited. In the study, male C57BL/6 mice at three different life phases (young, adult, and middle-aged) were simultaneously exposed to concentrated ambient PM2.5 or filtered air for 8 weeks using a whole-body inhalational exposure system. H&E staining and high-resolution respirometry were used to assess the size of adipocytes and mitochondrial function...

Colorectal cancer (CRC) is trending to be a major health problem throughout the world. Therapeutics with dual modes of action have shown latent capacity to create ideal anti-tumor activity. Signal transducer and activator of transcription 3 (STAT3) has been proved to be a potential target for the development of anti-colon cancer drug. In addition, modulation of tumor redox homeostasis through deploying exogenous reactive oxygen species (ROS)-enhancing agents has been widely applied as anti-tumor strategy. Thus, simultaneously targeting STAT3 and modulation ROS balance would offer a fresh avenue to combat CRC...

Aged nanoplastics (aged-NPs) have unique characteristics endowed by environmental actions, such as rough surface, high oxygen content. Although studies have highlighted the potential hazards of aged-NPs, limited research has provided strategies for aged-NPs pollution remediation. The dietary intervention of quercetin is a novel insight to address the health risks of aged-NPs. This study explored the impact of aged-NPs on intestinal barrier homeostasis at the environmentally relevant dose and investigated the alleviating effects of quercetin on aged-NPs toxicity through transcriptomics and molecular biology analysis...

STUDY OBJECTIVES: Increased reactive oxygen species associated with loss of mitochondrial function affect synaptic activity, which is an important mechanism underlying cognitive decline. This study assesses the role of mitochondrial proteins in neuron-derived exosomes (NDEs) on cognitive impairment in patients with obstructive sleep apnea (OSA) without dementia. METHODS: Analyses were conducted in 268 study participants with complete polysomnography data, cognitive tests, and important clinical data available...

BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator...

BACKGROUND: Tacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms. METHODS AND RESULTS: Thirty-two Sprague Dawley rats were treated with TAC (1.5 mg/kg/day, subcutaneously) and/or Lina (5 mg/kg/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity...

BACKGROUND: Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence...

Repeated sevoflurane exposure in neonatal mice can leads to neuronal apoptosis and mitochondrial dysfunction. The mitochondria are responsible for energy production to maintain homeostasis in the central nervous system. The mitochondria-associated endoplasmic reticulum membrane (MAM) is located between the mitochondria and endoplasmic reticulum (ER), and it is critical for mitochondrial function and cell survival. MAM malfunction contributes to neurodegeneration, however, whether it is involved in sevoflurane-induced neurotoxicity remains unknown...

Cardiac arrest (CA) remains a leading cause of death, with suboptimal survival rates despite efforts involving cardiopulmonary resuscitation and advanced life-support technology. Post-resuscitation myocardial dysfunction (PRMD) is an important determinant of patient outcomes. Myocardial ischemia/reperfusion injury underlies this dysfunction. Previous reports have shown that ruthenium red (RR) has a protective effect against cardiac ischemia-reperfusion injury; however, its precise mechanism of action in PRMD remains unclear...

As a vital energy source for cellular metabolism and tissue survival, the mitochondrion can undergo morphological or positional change and even shuttle between cells in response to various stimuli and energy demands. Multiple human diseases are originated from mitochondrial dysfunction, but the curative succusses by traditional treatments are limited. Mitochondrial transplantation therapy (MTT) is an innovative therapeutic approach that is to deliver the healthy mitochondria either derived from normal cells or reassembled through synthetic biology into the cells and tissues suffering from mitochondrial damages and finally replace their defective mitochondria and restore their function...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD...

The interaction between endoplasmic reticulum (ER) and mitochondria has been shown to play a key role in hepatic steatosis during chronic obesity. β-nicotinamide mononucleotide (NMN) has been reported to regulate obesity, however, its molecular mechanism at the subcellular level remains unclear. Here, NMN improved liver steatosis and insulin resistance in chronic high-fat diet (HFD) mice. RNA-seq showed that compared with the liver of HFD mice, NMN intervention enhanced fat digestion and absorption and stimulated the cholesterol metabolism signaling pathways, while impaired insulin resistance and the fatty acid biosynthesis signaling pathways...

Numerous natural antioxidants have been developed into agents for neurodegenerative diseases (NDs) treatment. Rosmarinic acid (RA), an excellent antioxidant, exhibits neuroprotective activity, but its anti-NDs efficacy remains puzzling. Here, Caenorhabditis elegans models were employed to systematically reveal RA-mediated mechanisms in delaying NDs from diverse facets, including oxidative stress, the homeostasis of neural and protein, and mitochondrial disorders. Firstly, RA significantly inhibited reactive oxygen species accumulation, reduced peroxide malonaldehyde production, and strengthened the antioxidant defense system via increasing superoxide dismutase activity...