ArticleScience advances2025
FAF2 is a bifunctional regulator of peroxisomal homeostasis and saturated lipid responses.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- FAF1 and FAF2 enhance unfolding by p97-UFD1-NPL4 complex enabling rational design of p97 activators.The EMBO journal · 2026Article
- Crosstalk collapse: mitochondria-centric organelle network disruption in ovarian aging.Cell communication and signaling : CCS · 2026Review
- Mitochondrial dysfunction triggers a maladaptive peroxisomal response driving lipid accumulation.Redox biology · 2026Article
- Peroxisome-derived ether lipids regulate lysosomal exocytosis.The EMBO journal · 2026Article
- Faf2 is required for neural differentiation in embryonic neural progenitor cells.Frontiers in cell and developmental biology · 2026Article
- Intestine-specific Faf2 depletion ameliorates obesity and metabolic dysfunction-associated steatotic liver disease by impairing lipid absorption.International journal of biological sciences · 2026Article
- A UBH-UBX module amplifies p97/VCP's unfolding power to facilitate protein extraction and degradation.Nature communications · 2025Article
- The p97 ATPase and its adaptor UBXD8 maintain peroxisome pools by preventing pexophagy.The Journal of cell biology · 2025Article
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8 authors.
Funding
Abstract
Exposure to saturated fatty acids (SFAs), such as palmitic acid, can lead to cellular metabolic dysfunction known as lipotoxicity. Although canonical adaptive metabolic processes like lipid storage or desaturation are known cellular responses to saturated fat exposure, the link between SFA metabolism and organellar biology remains an area of active inquiry. We performed a genome-wide CRISPR knockout screen in human epithelial cells to identify modulators of SFA toxicity. The screen revealed peroxisomal proteins, especially those that affect ether lipid synthesis, as important regulators of lipotoxicity. We identified Fas-associated factor family member 2 (FAF2) as a critical bifunctional coregulator of peroxisomal and fatty acid biology. We further demonstrated the requirement of the ubiquitin-regulatory X (UBX) and UAS thioredoxin-like domains of FAF2 for peroxisomal protein abundance and SFA-induced cellular stress. Our work highlights the role of FAF2 in regulating peroxisomal abundance and function and the peroxisome as a key organelle in the cellular response to SFAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.