Biology subjects

Tavernarakis, N.

Publications and source records attributed to Tavernarakis, N..

3 recordsLinked to original sources

bioRxiv2026

A PPARγ-like signalling axis integrates lipid homeostasis and mitochondrial quality control to preserve neuronal integrity

Peroxisome proliferator-activated receptor gamma (PPAR{gamma}) is a central regulator of lipid metabolism and a critical mediator of neuroprotection, yet the mechanisms linking these functions remain unclear. Here, we identify the Caenorhabditis elegans nuclear receptor SEX-1 as a functional PPAR{gamma}-like regulator and define a pathway that coordinates lipid metabolism with mitochondrial homeostasis to preserve neuronal function. Integrating comparative genomics, multi-omics profiling, meta-analysis, and experimental validation, we show that SEX-1 orchestrates membrane sphingolipid metabolism, lipid droplet (LD) dynamics, and mitochondrial quality control through interconnected lipogenic and autophagic programs. Loss of sex-1 disrupts this metabolic network, resulting in aberrant LD accumulation, mitochondrial dysfunction, and widespread alterations in sphingolipid metabolism. These defects compromise the structural integrity and thermosensory function of amphid neurons during early adulthood, while the capacity of SEX-1 to restrict neuronal lipid droplet accumulation declines with age. Notably, genetic modulation of sphingolipid metabolic pathways rescues neuronal defects, establishing a causal link between lipid metabolic homeostasis and neuronal maintenance. Together, our findings identify a PPAR{gamma}-like signalling axis that integrates sphingolipid metabolism, organelle quality control, and neuronal homeostasis, providing a mechanistic framework for understanding how metabolic regulation promotes neuroprotection.

cell biology↗

bioRxiv2026

MORPHIS (MORPHological Interpretable Signature) captures heterogeneous treatment- and aging-related responses of single cells

Cell morphology encodes changes in cytoskeletal and organelle organization during disease, treatment, and aging, yet is often assessed qualitatively or through poorly interpretable feature sets extracted from microscopy images. Here we introduce MORPHIS (MORPHological Interpretable Signature), a machine learning framework on explainable, analytically rich features paired with statistical methodologies for robust and interpretable quantification of single-cell morphological signature. MORPHIS extracts compact, interpretable feature signatures that capture both perturbation-specific response magnitude and heterogeneous cellular responses. It accurately distinguishes treatment-specific morphological signatures of eight mechanistically distinct membrane-active and intracellular-targeting compounds in Caco-2 and HeLa cells elucidating conserved and divergent phenotypic responses among compound-classes, as well as ultrastructural nuclear alterations upon aging of C. elegans and quantifies heterogeneous single-cell fractional responses. By remaining cell-type and perturbation agnostic, MORPHIS provides a generalizable framework for quantifying morphological signatures across diverse biological contexts including pharmacological treatment or aging.

biophysics↗

bioRxiv2025

Condensate-Driven Triglyceride Depletion Links α-Synuclein to Mitochondrial Dysfunction

Inclusions of -Synuclein (Syn) characterize multiple age-related neurodegenerative diseases, including Parkinsons disease (PD) and Multiple System Atrophy (MSA). While interactions between Syn and lipids are known to contribute to Syn pathobiology, the precise cellular mechanisms that link lipids to Syn toxicity have yet to be elucidated. Through lipidomic profiling of Caenorhabditis elegans, we found that Syn progressively alters lipid metabolism in aging worms. Syn strongly reduces overall content of triacylglycerols (TAG) and disrupts the structure of lipid droplets (LD). These pathological changes depend on Syns properties to condensate and form inclusions. Apart from lowering TAG levels, Syn also increases the proportion of long-chain unsaturated fatty acids (LCUFAs). Consequently, genetic inhibition of LCUFA biosynthesis alleviates Syn-induced loss of C. elegans motility. Strikingly, bypassing lipid metabolic defects by supplementing Medium Chain Fatty Acids (MCFAs) restores the Syn-impaired mitochondrial response and rescues motility. These results link Syn condensation to impaired TAG metabolism, which reduces mitochondrial function and enhances overall toxicity. Together with the finding that plasma TAGs are lowered in Parkinson patient cohorts, these results suggest that restoring TAG metabolism could alleviate Syn-induced toxicity in Parkinsons and other age-related synucleinopathies.

cell biology↗