Regulation of cholesterol synthesis is very important: cholesterol is a component of cell membranes and a precursor of steroid hormones and bile acids, yet high levels of cholesterol can be toxic to cells and can contribute to heart disease. Cells in our body obtain cholesterol one of two ways – by taking it up from the bloodstream (via low-density lipoprotein or LDL) or by synthesizing it intracellularly. In Part 1 of his iBioSeminar, Dr. Russell DeBose-Boyd provides an overview of cholesterol regulation with a focus on HMG CoA reductase, the rate-limiting enzyme of cholesterol synthesis. He describes how the effects of statins, drugs prescribed to lower LDL in the blood, are blunted due to the disruption of feedback control of HMG CoA reductase. In the presence of sterols, HMG CoA reductase protein stability is decreased. This sterol-accelerated degradation of HMG CoA reductase is dependent on the enzyme’s membrane domain in a process known as ER-associated degradation (ERAD). DeBose-Boyd describes his lab’s contributions to a model of HMG CoA reductase ERAD in which polyubiquitination of the enzyme in response to sterols is mediated by two proteins, Insig-1 and Insig-2, leading to its ERAD by the 26S proteasome.
View the full talk with additional resources on our website
Regulation of Cholesterol Synthesis
Dr. Russell DeBose-Boyd describes cellular regulation of cholesterol synthesis, with a focus on endoplasmic reticulum-associated degradation (ERAD) of HMG CoA reductase. (Talk recorded in August 2019)
- Part 1: Feedback Regulation of HMG CoA ReductaseAudience:
- Student
- Researcher
- Educators of H. School / Intro Undergrad
- Educators of Adv. Undergrad / Grad
Duration: 00:23:47 - Part 2: Schnyder Corneal Dystrophy: Importance of UBIAD1 in Regulation of CholesterolAudience:
- Student
- Researcher
- Educators of Adv. Undergrad / Grad
Duration: 00:16:35