Mammalian copper homeostasis: physiological roles and molecular mechanisms.

In the past decade, evidence for the numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries of Cu involvement in cell signaling, autophagy, cell motility, differentiation, and regulated cell death (cuproptosis) have markedly extended the list of already known functions of Cu, such as a cofactor of essential metabolic enzymes, a protein structural component, and a regulator of protein trafficking. Novel and unexpected functions of Cu transporting proteins and enzymes have been identified, and new disorders of Cu homeostasis have been described.

Copper impairs the intestinal barrier integrity in Wilson disease.

In Wilson disease (WD), liver copper (Cu) excess, caused by mutations in the ATPase Cu transporting beta (ATP7B), has been extensively studied. In contrast, in the gastrointestinal tract, responsible for dietary Cu uptake, ATP7B malfunction is poorly explored. We therefore investigated gut biopsies from WD patients and compared intestines from two rodent WD models and from human ATP7B knock-out intestinal cells to their respective wild-type controls.

Slc25a3-dependent copper transport controls flickering-induced Opa1 processing for mitochondrial safeguard.

Following the Goldilocks principle, mitochondria size must be "just right." Mitochondria balance division and fusion to avoid becoming too big or too small. Defects in this balance produce dysfunctional mitochondria in human diseases.

Mechanism of Cu entry into the brain: many unanswered questions.

Brain tissue requires high amounts of copper (Cu) for its key physiological processes, such as energy production, neurotransmitter synthesis, maturation of neuropeptides, myelination, synaptic plasticity, and radical scavenging. The requirements for Cu in the brain vary depending on specific brain regions, cell types, organism age, and nutritional status. Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease, Wilson disease, Alzheimer's disease, Parkinson's disease, and others.

ATP7A-dependent copper sequestration contributes to termination of β-CATENIN signaling during early adipogenesis.

Objectives: Adipocyte fate determination is tightly regulated by extrinsic signaling pathways and intrinsic metabolic and morphologic changes that maintain adipose tissue function. Copper (Cu) homeostasis is required for the normal metabolism of mature adipocytes, whereas the role of Cu in adipogenesis is unclear.

Methods: To determine the role of Cu is adipocytes differentiation, we used 3T3-L1 adipocytes, immunocytochemistry, X-ray fluorescence, mass-spectrometry, pharmacological treatments, and manipulations of copper levels.