A PPAR-gamma counterpart protects worm neurons by coordinating lipids and mitochondria
Researchers show that SEX-1 regulates sphingolipid metabolism and mitochondrial quality control in Caenorhabditis elegans, but its protective activity declines with age.
bioRxiv · Tsagkari D et al. · Paper published 29 Sep 2026
In Caenorhabditis elegans, researchers identified the nuclear receptor SEX-1 as a functional counterpart to mammalian PPARγ. Using comparative genomics, multi-omics profiling, and experimental testing, the team investigated how this receptor coordinates metabolism to protect neurons. They found that SEX-1 orchestrates membrane sphingolipid metabolism, lipid droplet dynamics, and mitochondrial quality control via lipogenic and autophagic programs. Loss of sex-1 caused abnormal lipid droplet buildup, mitochondrial dysfunction, and altered sphingolipid metabolism. These disruptions harmed the structural integrity and thermosensory function of amphid sensory neurons during early adulthood. The ability of SEX-1 to restrict lipid droplet accumulation also declined with age. Genetically altering sphingolipid pathways rescued the neuronal defects, linking lipid homeostasis directly to neuron survival.
Why it matters
The decline of lipid regulation and organelle maintenance is closely linked to age-related neurodegeneration. Clarifying how PPARγ-like signaling integrates sphingolipids and mitochondrial quality highlights metabolic pathways that preserve neuronal resilience across the lifespan.
Caveats
This work was posted as a preprint and has not yet been peer-reviewed. The experiments were conducted entirely in nematodes, so the findings need to be tested in mammalian nervous systems.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
A PPARγ-like signalling axis integrates lipid homeostasis and mitochondrial quality control to preserve neuronal integrity
Tsagkari D, Markaki M, Zhang T et al.
bioRxiv · 29 Sep 2026 · Preprint, not yet peer-reviewed
- Relevance
- Relevant
- News value
- Notable
- Evidence
- Model organisms
- Status
- Preprint
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