cellular response to sterol depletion

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating deprivation of sterols. Sterols are a group of steroids characterized by the presence of one or more hydroxyl groups and a hydrocarbon side-chain in the molecule. [GOC:mah]

Cellular response to sterol depletion is a complex and intricate process involving a cascade of signaling events and transcriptional changes that ultimately aim to restore sterol homeostasis. Sterols, such as cholesterol, are essential components of cell membranes, playing crucial roles in maintaining membrane fluidity, integrity, and signaling pathways. When sterol levels decline, cells activate a series of mechanisms to sense and respond to this deficit. The initial step in this process involves the activation of the sterol regulatory element-binding protein (SREBP) pathway. SREBPs are transcription factors that control the expression of genes involved in sterol biosynthesis, uptake, and transport. Under normal conditions, SREBPs are bound to the endoplasmic reticulum (ER) membrane, where they are inactive. However, when sterol levels fall below a critical threshold, SREBPs are released from the ER and transported to the Golgi apparatus. In the Golgi, SREBPs are cleaved by proteases, generating a mature transcription factor that translocates to the nucleus. Once in the nucleus, SREBPs bind to specific DNA sequences known as sterol regulatory elements (SREs) located in the promoter regions of target genes. This binding initiates the transcription of genes involved in cholesterol biosynthesis, such as HMG-CoA reductase, which catalyzes the rate-limiting step in cholesterol synthesis. Furthermore, SREBPs also upregulate genes involved in the uptake of cholesterol from the bloodstream, such as the LDL receptor. These coordinated responses aim to increase sterol production and uptake to replenish cellular sterol levels. In addition to the SREBP pathway, other signaling pathways contribute to the cellular response to sterol depletion. For instance, the AMP-activated protein kinase (AMPK) pathway is activated by low sterol levels, promoting energy conservation and enhancing sterol biosynthesis. The activation of AMPK results in the phosphorylation and activation of key enzymes involved in sterol synthesis. Moreover, sterol depletion can also trigger the activation of the unfolded protein response (UPR), which is a cellular stress response mechanism that aims to alleviate stress in the ER caused by the accumulation of misfolded proteins. The UPR can lead to the upregulation of chaperone proteins that assist in protein folding and the degradation of misfolded proteins. In conclusion, the cellular response to sterol depletion is a multi-faceted process involving the activation of multiple signaling pathways and transcriptional changes. This intricate network of responses ensures that cells can maintain sterol homeostasis and survive in the face of sterol deprivation.'
```
"

Proteins (1)

Compounds (11)