Biology subjects

Chaurasia, M.

Publications and source records attributed to Chaurasia, M..

3 recordsLinked to original sources

bioRxiv2026

Targeting Autophagy Accelerates Intestinal Repair after Acute Ionizing Radiation

Radiation exposure induces systemic and cellular damage, contributing to acute radiation syndrome and long-term effects such as premature aging and carcinogenesis. At the cellular level, radiation triggers apoptosis, mutation, and transformation through oxidative damage and activation of pathways including ER stress-mediated autophagy. Autophagy plays a context-dependent dual role in stressed cells, but its contribution to intestinal recovery after acute radiation remains unclear. Here, we evaluated combinatorial radiomodification using gamma radiation (8 Gy) and autophagy modulators in whole-body irradiated C57BL/6 mice (8-10 weeks old, n = 10). Mice were treated with autophagy inducers or inhibitors and euthanized at 3-, 8-, and 30-day post-irradiation. The jejunal-ileal region was analyzed via antioxidant assays, immunoblotting, H&E staining, and immunohistochemistry. Radiation significantly altered oxidative stress and autophagy markers, including increased LC3-II and decreased SQSTM1/p62. Autophagy induction enhanced intestinal proliferation (as measured by Ki-67), whereas inhibition impaired regeneration. Rapamycin pretreatment improved survival and reduced markers of intestinal injury following 8 Gy total body irradiation (TBI), whereas chloroquine exacerbated several injury-associated parameters. Overall, our findings suggest that targeted modulation of autophagy is a promising strategy for alleviating radiation-induced gastrointestinal injury and provide mechanistic insights relevant to therapeutic development.

molecular biology↗

bioRxiv2025

Aberrant inheritance of extrachromosomal DNA amplifications promotes cancer evolution

Gene amplification in the form of extrachromosomal DNA (ecDNA) is a frequent driver in multiple cancer types. As ecDNA lack centromeres, their mitotic segregation does not follow traditional inheritance principles. However, the mechanisms that govern ecDNA fate following mitosis remain unclear. We found that ecDNA undergo numerical and structural optimization under increased selective pressure, with mitotic chromosomal tethering, or detachment, dictating ecDNA fate. When tethered, ecDNA aggregates promote uneven distribution into the newly formed daughter cells, thereby driving inter-cellular numerical heterogeneity and rapid increase of amplification under selective pressure. Mitotically detached ecDNA frequently encapsulate within micronuclei of variable size and content that appear to be highly fragile. Strikingly, ecDNA enclosed in very small micronuclei, which we term nanonuclei, are being actively degraded through autophagy. Together with ongoing structural rearrangements, nanonuclear ecDNA degradation promotes their structural evolution, which facilitates cancer cell adaptation. Our work highlights ecDNA aggregation, micronucleation, and degradation, as pivotal events in directing cancer genome evolution trajectories.

cancer biology↗

bioRxiv2025

TECPR2 maintains mitochondrial homeostasis in neurodegeneration

HSAN9 is a rare progressive neurodegenerative disease in children linked to bi-allelic loss-of-function mutations in the TECPR2 gene. TECPR2 is a multi-domain protein harboring N-terminal WD repeats and C-terminal TECPR repeats, followed by a functional LIR motif that serves in autolysosomal targeting. Here, we show that the lack of TECPR2 leads to impairment of mitophagy that can be recovered by the expression of its C-terminal domain. Accordingly, we uncover severe mitochondrial dysfunction and accumulation of mitochondrial content in primary fibroblasts derived from an HSAN9 patient, and in embryonic fibroblasts and dorsal root ganglia derived from an HSAN9 mouse model. Strikingly, these mitochondrial defects are mediated by a mitochondrial stress through activation of the integrated stress response (ISR), whereas mitochondrial function is recovered by pharmaceutical or genetic suppression of ISR. Our findings provide a new link between mitophagy and ISR in mitochondrial homeostasis during neurodegeneration.

cell biology↗