Itaconate drives mtRNA-mediated type I interferon production through inhibition of succinate dehydrogenase.

Itaconate is one of the most highly upregulated metabolites in inflammatory macrophages and has been shown to have immunomodulatory properties. Here, we show that itaconate promotes type I interferon production through inhibition of succinate dehydrogenase (SDH). Using pharmacological and genetic approaches, we show that SDH inhibition by endogenous or exogenous itaconate leads to double-stranded mitochondrial RNA (mtRNA) release, which is dependent on the mitochondrial pore formed by VDAC1.

Succinate Dehydrogenase and Human Disease: Novel Insights into a Well-Known Enzyme.

Succinate dehydrogenase (also known as complex II) plays a dual role in respiration by catalyzing the oxidation of succinate to fumarate in the tricarboxylic acid (TCA) cycle and transferring electrons from succinate to ubiquinone in the mitochondrial electron transport chain (ETC). Owing to the privileged position of SDH/CII, its dysfunction leads to TCA cycle arrest and altered respiration. This review aims to elucidate the widely documented profound metabolic effects of SDH/CII deficiency, along with the newly unveiled survival mechanisms in SDH/CII-deficient cells.

SARS-CoV-2 Viroporin E Induces Ca Release and Neuron Cell Death in Primary Cultures of Rat Hippocampal Cells Aged In Vitro.

The COVID-19 pandemic was caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which may lead to serious respiratory, vascular and neurological dysfunctions. The SARS-CoV-2 envelope protein (E protein) is a structural viroporin able to form ion channels in cell membranes, which is critical for viral replication. However, its effects in primary neurons have not been addressed.

The mitochondrial signature of cultured endothelial cells in sepsis: Identifying potential targets for treatment.

Sepsis is the most common cause of death from infection in the world. Unfortunately, there is no specific treatment for patients with sepsis, and management relies on infection control and support of organ function. A better understanding of the underlying pathophysiology of this syndrome will help to develop innovative therapies.

Development of a novel in vitro model to study the modulatory role of the respiratory complex I in macrophage effector functions.

Increasing evidence demonstrate that the electron transfer chain plays a critical role in controlling the effector functions of macrophages. In this work, we have generated a Ndufs4-/- murine macrophage cell lines. The Ndufs4 gene, which encodes a supernumerary subunit of complex I, is a mutational hotspot in Leigh syndrome patients.

Association between RS3763040 polymorphism of the AQP4 and idiopathic intracranial hypertension in a Spanish Caucasian population.

Background: Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure of unknown aetiology. Principal symptoms are headache, visual disturbances, and obesity, together with elevated intracranial pressure. Unspecified MRI, despite normal ventricle size, suggests alterations in the water flux cellular mediated by the brain water channel aquaporin-4 (AQP4).

The mitochondrial succinate dehydrogenase complex controls the STAT3-IL-10 pathway in inflammatory macrophages.

The functions of macrophages are tightly regulated by their metabolic state. However, the role of the mitochondrial electron transport chain (ETC) in macrophage functions remains understudied. Here, we provide evidence that the succinate dehydrogenase (SDH)/complex II (CII) is required for respiration and plays a role in controlling effector responses in macrophages.

Differential Ca responses and store operated Ca entry in primary cells from human brain tumors.

Brain tumors comprise a large series of tumor cancer from benign to highly malignant gliomas and metastases from primary tumors outside the brain. Intracellular Ca homeostasis is involved in a large series of cell functions including cell proliferation, migration, and cell death. Store-operated Ca entry (SOCE), the most important Ca entry pathway in non-excitable cells, is involved in cell proliferation and migration and enhanced in tumor cells from breast cancer, colon cancer and cell lines derived from glioblastoma but there are almost no studies in human primary glioblastoma cells or other brain tumors.

Marine Heterocyclic Compounds That Modulate Intracellular Calcium Signals: Chemistry and Synthesis Approaches.

Intracellular Ca plays a pivotal role in the control of a large series of cell functions in all types of cells, from neurotransmitter release and muscle contraction to gene expression, cell proliferation and cell death. Ca is transported through specific channels and transporters in the plasma membrane and subcellular organelles such as the endoplasmic reticulum and mitochondria. Therefore, dysregulation of intracellular Ca homeostasis may lead to cell dysfunction and disease.

Store-operated Ca entry and Ca responses to hypothalamic releasing hormones in anterior pituitary cells from Orai1-/- and heptaTRPC knockout mice.

Store operated Ca entry (SOCE) is the most important Ca entry pathway in non-excitable cells. However, SOCE can also play a pivotal role in excitable cells such as anterior pituitary (AP) cells. The AP gland contains five different cell types that release six major AP hormones controlling most of the entire endocrine system.