SPFH Protein Superfamily (SPFH 蛋白家族)

The SPFH protein family, including Stomatin, Prohibitin, Flotillin, and HflK/C. They share a common SPFH domain that plays a central role in the formation and maintenance of local microenvironments within the cell membrane. These proteins are distributed across various membrane systems within the cell, including the plasma membrane, endoplasmic reticulum, Golgi apparatus, and mitochondria.
SPFH proteins interact with other membrane protein complexes through their transmembrane regions, influencing the physical properties and signal transduction capabilities of the cell membrane. For example, Flotillin acts as an assembly platform in cell signal transduction, regulating processes including receptor-mediated endocytosis and the activation of signaling molecules. Prohibitin plays a key role in maintaining mitochondrial structure and function, affecting cell growth and survival. Additionally, SPFH proteins regulate the aggregation and activation of membrane-associated signaling molecules, participating in various physiological cell responses. For instance, SPFH proteins interact with cytoskeletal elements and secondary messenger systems like cAMP, affecting cell migration, proliferation, and apoptosis.
Abnormal expression of SPFH proteins is associated with various diseases. The most studied SPFH proteins, prohibitins, have already been targeted by different families of small molecules to induce anticancer, cardioprotective, anti-inflammatory, antiviral, and antiosteoporotic activities. Overexpression of Flotillin is related to neurodegenerative diseases such as Alzheimer's, potentially affecting neuronal signal transmission and intercellular communication. Moreover, the regulatory mechanisms of SPFH proteins show potential therapeutic value in inflammatory responses and metabolic diseases, especially in their roles in regulating immune cell functions and lipid metabolism.
The SPFH protein family is crucial for maintaining the integrity and functionality of cell membranes and also provides strategies for studying the mechanisms of related diseases^[1][2].