ER stress-associated transcription factor CREB3 is essential for normal Ca, ATP, and ROS homeostasis.

In mammalian cells, mitochondrial respiration produces reactive oxygen species (ROS) such as superoxide (O), which is then converted by the SOD1 enzyme into hydrogen peroxide (HO), the predominant form of cytosolic ROS. ROS at high levels can be toxic, but below this threshold are important for physiological processes acting as a second messenger similar to Ca. Mitochondrial Ca influx from the ER increases ATP and ROS production, while ATP and ROS can regulate Ca homeostasis, leading to an intricate interplay between Ca, ROS, and ATP synthesis.

Transcription factor CREB3 is a potent regulator of high-fat diet-induced obesity and energy metabolism.

Background: The endoplasmic reticulum senses alterations to cellular homeostasis that activates the unfolded protein response (UPR). UPR proteins are known to aid in regulating glucose and lipid metabolism. CREB3 is a UPR-associated transcription factor whose potential role in regulating energy metabolism remains unclear.

Modeling neuronal consequences of autism-associated gene regulatory variants with human induced pluripotent stem cells.

Genetic factors contribute to the development of autism spectrum disorder (ASD), and although non-protein-coding regions of the genome are being increasingly implicated in ASD, the functional consequences of these variants remain largely uncharacterized. Induced pluripotent stem cells (iPSCs) enable the production of personalized neurons that are genetically matched to people with ASD and can therefore be used to directly test the effects of genomic variation on neuronal gene expression, synapse function, and connectivity. The combined use of human pluripotent stem cells with genome editing to introduce or correct specific variants has proved to be a powerful approach for exploring the functional consequences of ASD-associated variants in protein-coding genes and, more recently, long non-coding RNAs (lncRNAs).