The C. elegans PAQR-2 and IGLR-2 membrane homeostasis proteins are uniquely essential for tolerating dietary saturated fats

• How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we report the first whole-organism (Caenorhabditis elegans) forward genetic screen to identify genes essential for tolerance to dietary saturated fatty acids (SFAs). We found that only the PAQR-2/IGLR-2 pathway, homologous to the human adiponectin receptor 2 (AdipoR2) pathway, is uniquely essential to prevent SFA-mediated toxicity. When provided a SFA-rich diet, worms lacking either protein accumulate an excess of SFAs in their membrane phospholipids, which is accompanied by membrane rigidification. Additionally, we used fluorescence resonance energy transfer (FRET) to show that the interaction between PAQR-2 and IGLR-2 is regulated by membrane fluidity, suggesting a mechanism by which this protein complex senses membrane properties. We also created versions of PAQR-2 that lacked parts of the cytoplasmic N-terminal domain and showed that these were still functional, though still dependent on the interaction with IGLR-2. We conclude that membrane homeostasis via the PAQR-2/IGLR-2 fluidity sensor is the only pathway specifically essential for the non-toxic uptake of dietary SFAs in C. elegans.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

Membrane lipids

Membrane fluidity

Diet and dietary lipids

Fatty

acid/desaturase

Molecular biology/genetics

Cell biology

Lipotoxicity

Lipidomics

AdipoR2

C. elegans

Biochemistry & Molecular Biology

Biophysics

Cell Biology

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