START ships lipids across interorganelle space

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Steroidogenic Acute Regulatory protein (StAR)-related lipid transfer (START) proteins are characterized by a conserved domain responsible for lipid binding and transport.
• These proteins are crucial for various physiological processes, including lipid metabolism, signaling, and intracellular lipid transfer.

Purpose of the Study:

• To review the structure, function, and biological roles of the START protein family.
• To highlight the significance of START proteins in diverse cellular processes and their implications in human diseases.

Main Methods:

• Bioinformatic analysis of START protein homology and subfamily classification.
• Review of existing literature on START protein structure, function, and localization.
• Analysis of the role of additional domains in START protein function.

Main Results:

• Mammalian START proteins are classified into six subfamilies based on homology, each with specialized lipid-binding capabilities.
• START proteins exhibit distinct expression profiles and subcellular localizations, contributing to their varied biological functions.
• START proteins are implicated in lipid transfer, metabolism, signaling modulation, and are linked to genetic disorders, autoimmune diseases, and cancers.

Conclusions:

• The START domain's lipid-binding pocket and associated domains facilitate efficient lipid exchange.
• START proteins play critical roles in maintaining cellular lipid homeostasis and signaling pathways.
• Dysregulation of START proteins contributes to various pathological conditions, underscoring their clinical relevance.