Biology subjects

Zechini, L.

Publications and source records attributed to Zechini, L..

3 recordsLinked to original sources

bioRxiv2026

Intestinal bacteria hijack an evolutionarily conserved epithelial repair signal

Apoptosis in the gut triggers an expansion in the Enterobacteriaceae family of bacteria, causing both prolonged tissue injury and delayed repair. However, the mechanisms linking the Enterobacteriaceae bloom and subsequent deleterious tissue response are relatively unknown. Here, we establish purines as a major component of the apoptotic secretome that are consumed by bacteria. Explicitly, we identify hypoxanthine as a critical metabolite that is taken up and metabolised by both pathogenic and commensal species within the Enterobacteriaceae family. Epithelial cells release hypoxanthine into the extracellular space during early stages of apoptosis via the upregulation of equilibrative nucleoside transporters 1/2 (ENT1/2). Critically, beyond simply linking host and microbe, we delineate a connection between the release of hypoxanthine from the dying cell and the ability of the host to repair damaged epithelial tissue. Hypoxanthine is a potent promoter of epithelial cell repair in both gut and skin across the phylogenetic tree including humans, mice, zebrafish, and fruit flies and promotes similar ATP production and cellular proliferation in eukaryotic and microbial recipients. Thus, the preferential utilisation of hypoxanthine by the Enterobacteriaceae directly competes with the host for a core reparative signal.

microbiology↗

bioRxiv2025

Hepatocyte-like cells die via steroid hormone and nuclear receptor E75-mediated apoptosis

Metabolic organs must sustain physiological function while retaining the capacity for timely cell death. Systemic hormones play a key role in coordinating this balance, yet how they regulate cell death in vivo remains unclear. Here, we investigate hormone-regulated cell death in a metabolically specialised organ using Drosophila oenocytes, polyploid hepatocyte-like cells, as a tractable in vivo model. Using non-invasive longitudinal live imaging combined with oenocyte-specific genetic manipulation, we directly visualise larval oenocyte death during metamorphosis. We show that larval oenocyte loss is a dynamic, multistep process controlled by the steroid hormone ecdysone. We further identify the ecdysone-induced nuclear receptor E75 as a key regulator of the timing of cell death, as loss of E75 triggers premature oenocyte death. Oenocyte-specific manipulation of cell death pathways, together with live imaging using genetically encoded caspase reporters, provides direct evidence that larval oenocytes die by apoptosis. Together, this work defines how systemic hormonal signals regulate the timing of apoptosis in metabolically specialised polyploid cells and establishes oenocytes as a powerful in vivo system for studying cell death in metabolic organs.

developmental biology↗

bioRxiv2022

Piezo buffers mechanical stress via modulation of intracellular Ca2+ handling in the Drosophila heart

Throughout its lifetime the heart is buffeted continuously by dynamic mechanical forces resulting from contraction of the heart muscle itself and fluctuations in haemodynamic load and pressure. These forces are in flux on a beat-by-beat basis, resulting from changes in posture, physical activity or emotional state, and over longer timescales due to altered physiology (e.g. pregnancy) or as a consequence of ageing or disease (e.g. hypertension). It has been known for over a century of the hearts ability to sense differences in haemodynamic load and adjust contractile force accordingly1-4. These adaptive behaviours are important for cardiovascular homeostasis, but the mechanism(s) underpinning them are incompletely understood. Here we present evidence that the mechanically-activated ion channel, Piezo, is an important component of the Drosophila hearts ability to adapt to mechanical force. We find Piezo is a sarcoplasmic reticulum (SR)-resident channel and is part of a mechanism that regulates Ca2+ handling in cardiomyocytes in response to mechanical stress. Our data support a simple model in which Drosophila Piezo transduces mechanical force such as stretch into a Ca2+ signal, originating from the SR, that modulates cardiomyocyte contraction. We show that Piezo mutant hearts fail to buffer mechanical stress, have altered Ca2+ handling, become prone to arrhythmias and undergo pathological remodelling.

physiology↗