Advancing knowledge of human development, developmental disabilities, and neurodegenerative diseases.
The endoplasmic reticulum acetylation machinery has emerged as a new branch of the larger endoplasmic reticulum quality control system.
The endoplasmic reticulum acetylation machinery has emerged as a new branch of the larger endoplasmic reticulum quality control system.
Cytosolic citrate is imported from the mitochondria by SLC25A1, and from the extracellular milieu by SLC13A5. In the cytosol, citrate is used by ACLY to generate acetyl-CoA, which can then be exported to the endoplasmic reticulum (ER) by SLC33A1.
Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), Charcot-Marie-Tooth disease, and retinitis pigmentosa all have different manifestations and affect different body functions, but they are all connected by one mechanism: neurodegeneration.
Autism spectrum disorder (ASD) is an intricate and complicated diagnosis. The spectrum of presentations and severity is as expansive as the theorized causes. Autism’s complexity and breadth of impacts on a person’s life means that it has a multitude of facets to investigate.
Endoplasmic reticulum-based Nɛ-lysine acetylation serves as an important protein quality control system for the secretory pathway.
While researchers believe there is no single cause for Autism Spectrum Disorder (ASD), two new studies by Luigi Puglielli, MD, PhD, reveal a new potential genetic connection as a cause of the condition.
A new study from the lab of UW-Madison professor of medicine Luigi Puglielli, MD, PhD, opens a door to potential treatments for diseases of age, such as Alzheimer’s disease, by defining the roles of two enzymes that are imperative to protein production.
Nε-lysine acetylation in the ER is an essential component of the quality control machinery. ER acetylation is ensured by a membrane transporter, AT-1/SLC33A1, which translocates cytosolic acetyl-CoA into the ER lumen, and two acetyltransferases, ATase1 and ATase2, which acetylate nascent polypeptides within the ER lumen. Dysfunctional AT-1, as caused by gene mutation or duplication events, results in severe disease phenotypes.
Nε-lysine acetylation of nascent glycoproteins within the endoplasmic reticulum (ER) lumen regulates the efficiency of the secretory pathway. The ER acetylation machinery consists of the membrane transporter, acetyl-CoA transporter 1 (AT-1/SLC33A1), and two acetyltransferases, ATase1/NAT8B and ATase2/NAT8. Dysfunctional ER acetylation is associated with severe neurological diseases with duplication of AT-1/SLC33A1 being associated with autism spectrum disorder, intellectual disability, and dysmorphism.
