ER and Mitochondrial Stress Signaling in Nuclear Reprogramming: Mechanisms Linking Organelle Dysfunction to Aging and Disease.

Stress signaling from the endoplasmic reticulum (ER) and mitochondria is increasingly recognized as a central regulator of nuclear gene expression, chromatin organization, and long-term cellular adaptation. While ER stress and unfolded protein response (UPR) pathways, as well as mitochondrial retrograde signaling, have been extensively studied individually, the mechanisms by which these organelle-derived signals converge on the nucleus to reprogram transcription remain incompletely understood. Recent studies suggest that stress signals originating in cellular organelles can directly reshape nuclear transcriptional programs and chromatin states, highlighting a critical but still poorly defined layer of intracellular communication.This Research Topic aims to explore how stress signals originating from the ER and mitochondria drive nuclear reprogramming through transcription factor activation or relocalization, chromatin remodeling, epigenetic regulation, and stress-associated nuclear modifications. Understanding these pathways is essential for clarifying how cells adapt to organelle dysfunction and how such adaptive responses influence long-term cellular identity and function.The collection seeks to address several key questions in the field: How do ER and mitochondrial stress pathways communicate with the nucleus beyond canonical homeostatic responses? Which transcription factors, chromatin regulators, and signaling intermediates mediate the transition from organelle stress to altered nuclear gene expression? How do spatial interactions between organelles and the nucleus influence these regulatory events? Finally, under what conditions do these adaptive programs become maladaptive, contributing to aging-associated decline, neurodegeneration, metabolic dysfunction, developmental defects, and related disease states?We welcome original research articles, reviews, and methodological studies that provide mechanistic insight into ER stress signaling, UPR pathways, mitochondrial retrograde signaling, and their downstream effects on nuclear organization and transcriptional control. Topics of interest include PERK, IRE1, and ATF6 signaling in nuclear reprogramming; relocalization of mitochondria-associated transcription factors to the nucleus; stress-induced chromatin remodeling and epigenetic plasticity; PARylation and other stress-linked nuclear regulatory events; crosstalk between ER and mitochondrial stress responses; and the contribution of these pathways to aging, neurodegeneration, and related disorders.We particularly encourage studies employing advanced experimental systems and emerging technologies, including genetically tractable model organisms, mammalian cell lines, organoids, and human iPSC-based models. Contributions using live-cell imaging, spatial and super-resolution microscopy, single-cell approaches, multi-omics analyses, and integrative systems biology strategies are especially welcome, as these approaches provide powerful tools to dissect the dynamic communication between organelles and the nucleus during cellular stress. Topic editors: Sahana Mitra, Abhijnan Chattopadhyay, DIPAN ROY Source: https://www.frontiersin.org/research-topics/78121/er-and-mitochondrial-stress-signaling-in-nuclear-reprogramming-mechanisms-linking-organelle-dysfunction-to-aging-and-disease