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.
Luigi Puglielli
Neurodegeneration research at the Waisman Center from gene to organelle to cell to brain
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.
Understanding autism from the minute to the masses: Autism research at the Waisman Center
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.
Luigi Puglielli, MD, PhD – Slide of the Week
Endoplasmic reticulum-based Nɛ-lysine acetylation serves as an important protein quality control system for the secretory pathway.
Malfunctioning quality control pathway in neurons may be a cause of autism spectrum disorder
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.
The identities of enzymes: study further defines the function of a potential target for Alzheimer’s therapy
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.
Luigi Puglielli, MD, PhD – Slide of the Week
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.
Luigi Puglielli, MD, PhD – Slide of the Week
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.
Luigi Puglielli, MD, PhD – Slide of the Week
Mutations and duplication events in AT-1/SLC33A1 are highly pleiotropic and have been linked to diseases such as spastic paraplegia, developmental delay, autism spectrum disorder, intellectual disability, propensity to seizures, and dysmorphism.
Scientists discover cause of aging-related disease in mice, then reverse its symptoms
In a study published in Aging Cell, researchers at the University of Wisconsin–Madison show that mice making too much of a human protein called AT-1 show signs of early aging and premature death, which are …