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Updated: Jun 4, 2026
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PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions
Published on: July 27, 2017
Seipin: A central lipid rheostat.
Abdou Rachid Thiam1, Maxime Carpentier1
1Laboratoire de Physique de l'École Normale Supérieure, ENS, Université PSL, CNRS Sorbonne Université, Université Paris-Diderot, Sorbonne Paris Cité, Paris, France.
The Journal of Cell Biology
|June 3, 2026
Summary
Seipin, a flexible protein scaffold, regulates cellular lipid homeostasis and metabolic flux by sensing lipid composition. Its dynamic structure and interactions control lipid pathways, maintaining metabolic stability.
Area of Science:
- Cell Biology
- Metabolic Regulation
- Lipid Homeostasis
Background:
- Seipin is an oligomeric scaffold regulating lipid homeostasis beyond lipid droplet biogenesis.
- It senses local lipid composition and membrane features to direct metabolic flux.
- Seipin is primarily ER-resident but can relocate to mitochondria-associated membranes.
Purpose of the Study:
- To elucidate the regulatory role of seipin in cellular lipid homeostasis.
- To understand how seipin's conformational flexibility influences its function.
- To propose a unified model for seipin's function as a proteolipid regulatory hub.
Main Methods:
- Conformational analysis of seipin.
- Investigation of seipin interactions with cofactors and lipid ligands.
- Study of seipin localization and function at ER-LD and mitochondria-associated membranes.
Main Results:
- Seipin adopts multiple conformations influenced by cofactors and lipids, conferring functional versatility.
- Seipin regulates lipid synthesis, turnover, and Ca2+ levels at mitochondria-associated membranes.
- Seipin dysfunction leads to lipid imbalance and metabolic/neuronal disorders.
Conclusions:
- Seipin acts as a multistate proteolipid regulatory hub, adjusting its structure and interactome dynamically.
- It functions as a rheostat controlling lipid pathway decisions in response to metabolic signals.
- Seipin is crucial for interorganelle communication and maintaining metabolic stability.
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