Uniporter

BACKGROUND: Calcium (Ca2+ ) uptake by mitochondria occurs via the mitochondrial Ca2+ uniporter. Mitochondrial Ca2+ uniporter exists as a complex, regulated by 3 MICU (mitochondrial Ca2+ uptake) proteins localized in the intermembrane space: MICU1, MICU2, and MICU3. Although MICU3 is present in the heart, its role is largely unknown. METHODS: We used CRISPR-Cas9 to generate a mouse with global deletion of MICU3 and an adeno-associated virus (AAV9) to overexpress MICU3 in wild-type mice...

Uniportal video-assisted thoracoscopic surgery (UVATS) segmentectomy has emerged as an effective approach for managing early-stage non-small-cell lung cancer (NSCLC). Compared to conventional open and thoracoscopic surgeries, this minimally invasive surgical technique offers multiple benefits, including reduced postoperative discomfort, shorter hospital stays, expedited recovery, fewer complications, and superior cosmetic outcomes. Particularly advantageous in preserving lung function, UVATS segmentectomy is a compelling option for patients with compromised lung capabilities or limited pulmonary reserve...

BACKGROUND: The postoperative outcomes of suction drainage versus non-suction drainage after uniportal video-assisted thoracoscopic surgery (UniVATS) come with little consensus. This study aimed to prospectively compare the postoperative outcomes of suction drainage versus non-suction drainage in patients who underwent UniVATS. METHODS: Between October 2022 and January 2023, patients undergoing UniVATS were prospectively enrolled. The choice of drainage strategy (suction or non-suction) was at the surgeon's discretion...

OBJECTIVE: The objective of this study is to elucidate the influence of MCU on the clinical pathological features of GC patients, to investigate the function and mechanism of the mitochondrial calcium uptake transporter MCU in the initiation and progression of GC, and to explore its impact on the metabolic pathways and biosynthesis of mitochondria. The ultimate goal is to identify novel targets and strategies for the clinical management of GC patients. METHODS: Tumor and adjacent tissue specimens were obtained from 205 patients with gastric cancer, and immunohistochemical tests were performed to assess the expression of MCU and its correlation with clinical pathological characteristics and prognosis...

Diatoms are important primary producers in marine and freshwater environments, but little is known about the signalling mechanisms they use to detect changes in their environment. All eukaryotic organisms use Ca2+ signalling to perceive and respond to environmental stimuli, employing a range of Ca2+ -permeable ion channels to facilitate the movement of Ca2+ across cellular membranes. We investigated the distribution of different families of Ca2+ channels in diatom genomes, with comparison to other members of the stramenopile lineage...

Oxidative phosphorylation is regulated by mitochondrial calcium (Ca2+ ) in health and disease. In physiological states, Ca2+ enters via the mitochondrial Ca2+ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca2+ homeostasis is critical: insufficient Ca2+ impairs stress adaptation, while Ca2+ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca2+ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia...

The mitochondrial calcium (Ca2+ ) uniporter (MCU) complex is regulated via integration of the MCU dominant negative beta subunit (MCUb), a low conductance paralog of the main MCU pore forming protein. The MCU amino (N)-terminal domain (NTD) also modulates channel function through cation binding to the MCU regulating acidic patch (MRAP). MCU and MCUb have high sequence similarities, yet the structural and functional roles of MCUb-NTD remain unknown. Here, we report that MCUb-NTD exhibits α-helix/β-sheet structure with a high thermal stability, dependent on protein concentration...

INTRODUCTION: Lung cancer is a serious health problem with a high mortality rate. In the context of surgical management, minimally invasive approaches, including uniportal thoracoscopic techniques, offer potential benefits such as faster recovery and increased patient cooperation. The aim of this study was to compare the accessibility of the mediastinal lymph nodes between uniportal and multiportal thoracoscopic approaches and to verify whether the use of the uniportal approach affects the radicality of the lymphadenectomy...

INTRODUCTION: Although primary spontaneous pneumothorax is a common disease in young adults, each thoracic surgery department performs different procedures for its management. AIM: The optimal time of postoperative mobilization is not yet standardized in lung surgery. MATERIAL AND METHODS: This study included male patients with a primary spontaneous pneumothorax who underwent wedge resection of the upper lobe of the lungs via uniportal video-assisted thoracoscopic surgery...

Skeletal muscle has a major impact on total body metabolism and obesity, and is characterized by dynamic regulation of substrate utilization. While it is accepted that acute increases in mitochondrial matrix Ca2+ increase carbohydrate usage to augment ATP production, recent studies in mice with deleted genes for components of the mitochondrial Ca2+ uniporter (MCU) complex have suggested a more complicated regulatory scenario. Indeed, mice with a deleted Mcu gene in muscle, which lack acute mitochondrial Ca2+ uptake, have greater fatty acid oxidation (FAO) and less adiposity...

INTRODUCTION: This study aimed to investigate the effects of nicotine on the activation of pancreatic stellate cells (PSCs) and pancreatic fibrosis in chronic pancreatitis (CP), along with its underlying molecular mechanisms. METHODS: This was an in vivo and in vitro study. In vitro , PSCs were cultured to study the effects of nicotine on their activation and oxidative stress. Transcriptome sequencing was performed to identify potential signaling pathways involved in nicotine action...

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The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)-induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B-dependent hypertrophic and proinflammatory signaling...

UNLABELLED: Obesity is a public health crisis, and its prevalence disproportionately affects African Americans in the United States. Dysregulation of organelle calcium homeostasis is associated with obesity. The mitochondrial calcium uniporter ( MCU ) complex is primarily responsible for mitochondrial calcium homeostasis. Obesity is a multifactorial disease in which genetic underpinnings such as single-nucleotide polymorphisms (SNPs) may contribute to disease progression. The objective of this study was to identify genetic variations of MCU with anthropometric measurements and obesity in the All of Us Research Program...

The homeostasis of cellular calcium is fundamental for many physiological processes, while the calcium levels remain inhomogeneous within cells. During the onset of asthma, epithelial and inflammatory cells secrete platelet-derived growth factor (PDGF), inducing the proliferation and migration of airway smooth muscle (ASM) to the epidermal layer, narrowing the airway. The regulation of ASM cells by PDGF is closely related to the conduction of calcium signals. In this work, we generated subcellular-targeted FRET biosensors to investigate calcium regulation in the different compartments of ASM cells...

Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxide accumulation, plays a pivotal role in various pathological conditions, including neurodegenerative diseases. While reasonable evidence for ferroptosis exists, e.g., in Parkinson's disease or Alzheimer's disease, there are only a few reports on amyotrophic lateral sclerosis (ALS), a fast progressive and incurable neurodegenerative disease characterized by progressive motor neuron degeneration. Interestingly, initial studies have suggested that ferroptosis might be significantly involved in ALS...

INTRODUCTION: Mitochondrial calcium uniporter (MCU) is a central subunit of MCU complex that regulate the levels of calcium ions within mitochondria. A comprehensive understanding the implications of MCU in clinical prognostication, biological understandings and therapeutic opportunity of breast cancer (BC) is yet to be determined. OBJECTIVES: This study aims to investigate the role of MCU in predictive performance, tumor progression, epigenetic regulation, shaping of tumor immune microenvironment, and pharmacogenetics and the development of anti-tumor therapy for BC...

GATA is one of the prominent transcription factor families conserved among many organisms in eukaryotes and has different biological roles in many pathways, particularly in light regulation in plants. Although GATA transcription factors (TFs) have been identified in different crop species, their roles in abiotic stress tolerance have not been studied in potato. In this study, we identified 32 GATA TFs in potato ( Solanum tuberosum ) by in silico analyses, and expression levels of selected six genes were investigated in drought-tolerant (Sante) and sensitive (Agria) cultivars under light, drought, and combined (light + drought) stress conditions...

Epilepsy is one of the most common neurological disorders in the world. Common epileptic drugs generally affect ion channels or neurotransmitters and prevent the emergence of seizures. However, up to a third of the patients suffer from drug-resistant epilepsy, and there is an urgent need to develop new therapeutic strategies that go beyond acute antiepileptic (antiseizure) therapies towards therapeutics that also might have effects on chronic epilepsy comorbidities such as cognitive decline and depression. The mitochondrial calcium uniporter (MCU) mediates rapid mitochondrial Ca2+ transport through the inner mitochondrial membrane...

Dominant variants in WFS1 (wolframin ER transmembrane glycoprotein), the gene coding for a mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) resident protein, have been associated with Wolfram-like syndrome (WLS). In vitro and in vivo , WFS1 loss results in reduced ER to mitochondria calcium (Ca2+ ) transfer, mitochondrial dysfunction, and enhanced macroautophagy/autophagy and mitophagy. However, in the WLS pathological context, whether the mutant protein triggers the same cellular processes is unknown...