Biology subjects

Quinlan, L. R.

Publications and source records attributed to Quinlan, L. R..

3 recordsLinked to original sources

bioRxiv2026

Peroxiredoxin 6 limits mitochondrial peroxidation to prevent mitochondrial ER contact site assembly and inflammatory signalling following adaptive stress

Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme with peroxidase, calcium independent phospholipase A2 (aiPLA2) and lysophospatidylcholine acyltransterase (LPCAT) activities. Although PRDX6 can repair peroxidised phospholipids and help prevent ferroptosis, its role in the adaptive response to physiological oxidative stress remains unclear. In this study PRDX6 function was investigated using myoblasts exposed to an acute low concentration of H2O2 and Caenorhabditis elegans subjected to a swimming intervention. Mild oxidative stress promoted myogenesis and mitochondrial turnover in myoblasts, while exercise enhanced activity and longevity in C. elegans. The adaptive responses were associated with increased mitochondrial localisation of PRDX6. In contrast, loss of PRDX6 under mild stress conditions resulted in increased mitochondrial lipid peroxidation, enhanced mitochondrial ER contact sites (MERCS), mitochondrial calcium accumulation, release of mitochondrial DNA and activation of innate immune signalling pathways. Similar phenotypes were induced by the ferroptosis activator erastin and rescued by the lipid peroxyl scavenger Ferrostatin-1, indicating lipid peroxidation was the key triggering event. Furthermore, inhibition of mitochondrial calcium uptake in C. elegans prevented calcium overload and attenuated inflammatory signalling. Together, the results identify PRDX6 as a conserved regulator of mitochondrial adaptation to physiological oxidative stress, functioning to limit mitochondrial lipid peroxidation and prevent excessive MERCS assembly, mitochondrial calcium dysregulation and inflammatory activation.

cell biology↗

bioRxiv2025

Exercise Related microRNAs in C. elegans Regulate Calcium Homeostasis and Mitochondrial Dynamics: Conserved pathways, Divergent mircoRNAs

Exercise can help mitigate age-related muscle atrophy, promoting mitochondrial function, Ca2+ homeostasis and regulating gene expression. MicroRNAs (miRs) are crucial post-transcriptional regulators of gene expression, fine tuning protein levels to maintain cellular homeostasis. In C. elegans, a 5-day swimming regimen increased mitochondrial content, lifespan and fitness. Small RNA sequencing identified exercise specific miRs, including increased levels of cel-miR-57-5p and cel-miR-249-3p, and decreased cel-miR-72-3p and cel-miR-77-5p. mir-57 and mir-249 mutant strains had enhanced fertility, survival and lifespan, whereas mir-72 and mir-77 mutant strains had diminished fertility, survival and lifespan. Interestingly both miR-77 and mir-249 mutant strains had disrupted mitochondrial morphology and reduced fitness following exercise. The exercise related miRs identified in C. elegans did not have conserved mammalian orthologs. Exercise regulated mammalian miRs were identified from the literature including mmu-miR-181a-5p, mmu-miR-199a-5p and mmu-miR-378a-3p. Treatment of murine myoblasts with mmu-miR-181a-5p and mmu-miR-378a-3p enhanced mitochondrial content, autophagy markers and myogenesis, while mmu-miR-199a-5p impaired these processes. Exercise related miRs identified in C. elegans target genes regulating Ca2+ homeostasis such as ipp-5 (inositol Polyphosphate-5-phosphatase), sca-1 (Ca2+ transporting ATPase) and ncx-2 (mitochondrial Na+/Ca2+ antiporter). It was also confirmed that mmu-miR181a-5p (miR181) targets Inpp5a and antogmiR-181 (AM181) treatment decreased Ca2+ handling in myotubes. Similarly, mmu-miR-378a-3p and cel-miR-249-3p target Kinase Suppressor of Ras (Ksr1)/ksr-2, involved in the MAPK pathway. Despite direct conservation of exercise related miRs from nematodes to mammals there are common regulatory pathways, contributing to exercise-induced adaptations. Graphical abstractThe exercise related microRNAs (cel-miR-77-5p and cel-miR-249-3p) identified in C. elegans following a 5-day swimming protocol are not conserved in mammalians. However, the microRNAs identified share common gene targets regulating Ca2+ homeostasis and mitochondrial function, with previously identified exercise related microRNAs in murine models. The results highlight conserved regulatory adaptive mechanisms in response to exercise. O_FIG O_LINKSMALLFIG WIDTH=175 HEIGHT=200 SRC="FIGDIR/small/653755v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1da431forg.highwire.dtl.DTLVardef@6cdb70org.highwire.dtl.DTLVardef@ba9d76org.highwire.dtl.DTLVardef@1b7b481_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2020

Medial entorhinal spike clusters carry more finely tuned spatial information than single spikes

Many cells within the entorhinal cortex (EC) fire relatively infrequently, with the majority of their spikes separated by many hundreds of milliseconds. However, most cells are seen to occasionally fire two, three, or more spikes in quick succession. Recent evidence has shown that, in EC grid cells, "burstier" cells; cells that fire more of their spikes in bursts, have more well defined spatial characteristics than cells that fire fewer bursts. However, there is evidence that the window for considering related spikes in MEC could be as long as 100ms. Here, we divide the spikes fired by single cells into single spikes and "clusters" of spikes occuring within 100ms. We show that these burst "clusters" of spikes fired by cells in MEC convey more finely tuned spatial and directional information than the numerically more common single spikes. In addition, we find that introducing environmental uncertainty decreases the ratio of clusters fired to single spikes. Most crucially, we find that although single spikes are less spatially precise than clusters, they are more temporally precise - these spikes are more closely entrained to LFP theta than clusters. These findings demonstrate that clusters of spikes in EC convey more specific information about space than single spikes, may reflect "certainty" about spatial position and direction, and may represent a different firing "mode" in which intraregional communication is less relevant than interregional traffic.

neuroscience↗