Biology subjects

Cabianca, D. S.

Publications and source records attributed to Cabianca, D. S..

5 recordsLinked to original sources

bioRxiv2026

Mitochondrial stress signaling shapes the nuclear response to loss of the chromatin reader MRG-1

Perinuclear sequestration of heterochromatin is a major conserved feature of nuclear architecture. In Caenorhabditis elegans, the euchromatic reader MRG-1 was previously shown to promote peripheral localization of heterochromatin through an indirect mechanism that remained largely unknown. Here, we show that loss of MRG-1 activates a mitochondrial stress response. Genetic ablation of the PMK-3/MAPK mitochondrial stress regulator CBP-3 reveals that this pathway contributes to both detachment of a heterochromatic reporter from the nuclear periphery and approximately one-third of the transcriptional changes induced by mrg-1 depletion. Strikingly, loss of cbp-3 in MRG-1-deficient animals exacerbates mitochondrial dysfunction, fertility defects and embryonic lethality, indicating that part of the nuclear response induced by MRG-1 loss contributes to adaptation to mitochondrial stress rather than constituting a defect in heterochromatin 3D organization as previously thought. Together, our findings identify mitochondrial stress signaling as an unexpected mediator of the nuclear response to MRG-1 loss, demonstrating its contribution to gene regulation while supporting the idea that stress-induced changes in cellular physiology can also shape nuclear organization.

cell biology↗

bioRxiv2025

Methionine synthase reductase regulates heterochromatin independently of methionine synthesis through mitochondrial homeostasis

Metabolic enzymes can influence chromatin organization by modulating the availability of key metabolites, yet how specific metabolic reactions affect chromatin function remains poorly understood. Here, we show that in Caenorhabditis elegans, the methionine-cycle enzyme methionine synthase reductase (MTRR-l/MSR) regulates heterochromatin independently of methionine synthesis. Loss of MTRR-1, but not of the methionine synthase METR-l/MS, specifically reduces heterochromatic histone methylation, derepresses repetitive elements, and causes developmental delay. Multi-omics profiling revealed that mtrr-1 mutants activate transcriptional programs associated with mitochondrial stress and accumulate long-chain acylcamitines, indicating disrupted mitochondrial homeostasis. Functional assays confirmed altered mitochondrial respiration in mtrr-1 mutants, while genetic suppression of the PMK-3/MAPK mitochondrial retrograde signaling pathway partially restored repeat silencing. Consistently, direct perturbation of mitochondrial function was sufficient to induce heterochromatin derepression in wild type animals. Together, our results reveal a previously unrecognized mitochondria-to-chromatin axis controlled by the methionine-cycle enzyme MTRR-l/MSR, demonstrating that mitochondrial homeostasis is required for heterochromatin maintenance independently of canonical methionine metabolism.

cell biology↗

bioRxiv2025

HLH-30/TFEB is necessary for chromatin reorganization and maintenance of cell quiescence during starvation in C. elegans

Cellular quiescence is a metabolically active, non-proliferative state critical for tissue maintenance and regenerative capacity, with broad implications for aging and age-related diseases. In Caenorhabditis elegans, L1 developmental arrest upon hatching in the absence of food provides a robust in vivo model to study quiescence. Here, we investigate the roles of the transcription factors HLH-30/TFEB and DAF-16/FOXO during L1 arrest. We show that HLH-30 and DAF-16 collaborate to ensure survival under starvation, with reciprocal regulation of their subcellular localization and transcriptional activity. HLH-30 exerts broad transcriptional control during L1 arrest, modulating genes involved in chromosome organization and cell cycle progression. Profiling of chromatin spatial distribution reveals that HLH-30 is required for fasting-induced 3D chromatin reorganization. Loss of HLH-30 disrupts seam cell cycle arrest and leads to overactivation of the pioneer transcription factor BLMP-1, leading to premature initiation of developmental programs under starvation. Our findings uncover previously unrecognized functions of HLH-30 in genome architecture and quiescence regulation, highlighting conserved mechanisms of transcriptional control during nutrient deprivation with implications for aging and disease.

developmental biology↗

bioRxiv2024

SpotMAX: a generalist framework for multi-dimensional automatic spot detection and quantification

The analysis of spot-like structures is a widespread task in microscopy-based cell biology. Existing solutions are typically specific to single applications and do not use multi-dimensional information from 5D datasets. Therefore, experimental scientists often resort to subjective manual annotation. Here, we present SpotMAX, a generalist AI-driven framework for automated spot detection and quantification. SpotMAX leverages the full scope of multi-dimensional datasets with an easy-to-use interface and an embedded framework for cell segmentation and tracking. SpotMAX outperforms state-of-the-art tools, and in some cases, even expert human annotators. We applied SpotMAX across diverse experimental questions, ranging from meiotic crossover events in C. elegans to mitochondrial DNA dynamics in S. cerevisiae and telomere length in mouse stem cells, leading to new biological insights. With its flexibility in integrating AI workflows, we anticipate that SpotMAX will become the standard for spot analysis in microscopy data. Source code: https://github.com/SchmollerLab/SpotMAX

cell biology↗

bioRxiv2023

An mTOR/RNA pol I axis shapes chromatin architecture in response to fasting

Chromatin architecture is a fundamental mediator of genome function. Fasting is a major environmental cue across the animal kingdom. Yet, how it impacts on 3D genome organization is unknown. Here, we show that fasting induces a reversible and large-scale spatial reorganization of chromatin in C. elegans. This fasting-induced 3D genome reorganization requires inhibition of the nutrient-sensing mTOR pathway, a major regulator of ribosome biogenesis. Remarkably, loss of transcription by RNA Pol I, but not RNA Pol II nor Pol III, induces a similar 3D genome reorganization in fed animals, and prevents the restoration of the fed-state architecture upon restoring nutrients to fasted animals. Our work documents the first large-scale chromatin reorganization triggered by fasting and reveals that mTOR and RNA Pol I shape genome architecture in response to nutrients.

cell biology↗