CIDEA - Cell death inducing DFFA like effector A | Elisa - Clia - Antibody - Protein

Background

Cell Death Inducing DFFA-like Effector A (CIDEA) is a member of the CIDE family of proteins, which are involved in regulating apoptosis and lipid metabolism. CIDEA was initially identified for its role in apoptosis due to its sequence homology with the N-terminal domain of DNA fragmentation factor (DFF), a key player in apoptosis. However, subsequent studies have revealed that CIDEA has significant functions in lipid droplet biology and energy metabolism, particularly in adipocytes. CIDEA is primarily expressed in adipose tissue, liver, and to a lesser extent in other tissues such as the heart and skeletal muscle. Its dual role in promoting apoptosis and regulating lipid metabolism underscores its importance in both cell death pathways and metabolic homeostasis.

Protein Structure

CIDEA’s structure is characterized by several distinct features:

• N-terminal CIDE-N domain: This domain is conserved among CIDE family members and is crucial for the protein's pro-apoptotic activity. It mediates interactions with other proteins involved in apoptosis and lipid metabolism.
• C-terminal CIDE-C domain: This domain is essential for lipid droplet binding and lipid transfer activities. It facilitates the association of CIDEA with lipid droplets in adipocytes.
• Amphipathic helix: Located within the CIDE-C domain, this helix is critical for the interaction of CIDEA with lipid membranes and droplets.

Classification and Subtypes

CIDEA belongs to the CIDE protein family, which includes:

• CIDEA: Primarily involved in apoptosis and lipid metabolism.
• CIDEB: Similar to CIDEA but with distinct tissue distribution and functions, particularly in the liver.
• CIDEC (also known as Fsp27): Mainly expressed in adipose tissue and plays a crucial role in lipid droplet formation and maintenance.

Function and Biological Significance

CIDEA performs several critical functions:

• Regulation of Apoptosis: Initially identified for its pro-apoptotic activity, CIDEA promotes apoptosis through its interaction with DFF45 (ICAD), facilitating the release of DFF40 (CAD), which degrades DNA during apoptosis.
• Lipid Droplet Biology: CIDEA regulates lipid droplet formation, growth, and lipid storage. It promotes lipid droplet fusion, increasing the size of lipid droplets and enhancing lipid storage capacity in adipocytes.
• Energy Metabolism: By regulating lipid droplet dynamics, CIDEA influences energy storage and expenditure. Its activity is crucial for maintaining metabolic homeostasis, particularly under conditions of energy surplus or deficit.
• Thermogenesis: In brown adipose tissue, CIDEA plays a role in the regulation of thermogenic programs, contributing to the body's ability to generate heat through the metabolism of stored lipids.

Clinical Issues

Alterations in CIDEA function or expression are implicated in several metabolic and apoptotic disorders:

• Obesity: Dysregulation of CIDEA expression in adipose tissue can contribute to abnormal lipid storage and metabolic dysfunction, leading to obesity and related metabolic disorders.
• Diabetes: Altered CIDEA activity can affect lipid metabolism and insulin sensitivity, contributing to the development of type 2 diabetes.
• Non-Alcoholic Fatty Liver Disease (NAFLD): Given its role in lipid metabolism, aberrant CIDEA expression in the liver can lead to excessive lipid accumulation, promoting NAFLD.
• Cancer: While primarily studied for its metabolic roles, CIDEA's involvement in apoptosis suggests that its dysregulation could influence cancer cell survival and proliferation.

Summary

CIDEA is a multifunctional protein with critical roles in both apoptosis and lipid metabolism. Its structure includes N-terminal and C-terminal domains essential for its pro-apoptotic and lipid droplet regulatory functions, respectively. By regulating lipid droplet formation and energy metabolism, CIDEA helps maintain metabolic homeostasis and influences energy storage and expenditure. Dysregulation of CIDEA is associated with various metabolic diseases, including obesity, diabetes, and NAFLD, as well as potential implications in cancer. Understanding the mechanisms by which CIDEA balances its roles in apoptosis and lipid metabolism continues to be an important area of research with significant therapeutic potential.