Organelle ion transport in the endoplasmic reticulum and mitochondria: biophysical mechanisms, regulation, and disease

Ion transport within the endoplasmic reticulum (ER) and mitochondria is fundamental to cellular function and integrity, orchestrating key processes such as metabolism, signaling, and survival. These organelles serve as pivotal sites for the regulation of calcium (Ca²⁺) and magnesium (Mg²⁺) gradients, which underpin diverse phenomena from ATP synthesis and protein folding to the activation of stress response pathways and apoptosis. The coordinated activity of a wide array of channels, transporters, and exchangers ensures precise control of ion fluxes within and between organelles, finely tuning cellular physiology. In spite of impressive advancements, significant questions remain about the quantitative mechanisms guiding ion transport, the principles of selectivity and regulation, and the interplay between ionic gradients, metabolism, and membrane potential. Important debates persist around the nature of microdomains, the coupling mechanisms between the ER and mitochondria, and the ways in which transport dysfunction leads to pathologies such as neurodegeneration and metabolic disease. While techniques such as genetically encoded ion sensors, super-resolution imaging, and high-throughput biophysical modeling are pushing the boundaries of what can be measured and predicted, critical gaps exist in our mechanistic and quantitative understanding of these transport processes, especially in living cells.This Research Topic aims to consolidate and showcase innovative research that advances our understanding of organelle ion transport with a particular focus on the ER and mitochondria. The primary objective is to elucidate the molecular and biophysical basis of ion channel and transporter function, regulatory networks that control organelle ionic composition, and the downstream effects on cellular signaling and metabolism. We seek to address how alterations in these processes contribute to disease, and how emerging methodologies—including advanced imaging, quantitative biophysics, and computational modeling—are enabling new insights. A key goal is to bring into dialogue approaches spanning experimental, theoretical, and data-driven domains, fostering a platform for comprehensive mechanistic and physiological exploration of organelle ion transport.This Research Topic will center on quantitative, mechanistic, and disease-related perspectives of ER and mitochondrial ion transport while encouraging the integration of advanced methodologies. To gather further insights into the mechanisms and regulation of ion flux at organelle membranes, we welcome articles addressing, but not limited to, the following themes:Ion channels, transporters, and exchangers in the ER and mitochondriaMechanisms of Ca²⁺ and Mg²⁺ transport and signaling at organelle membranesBiophysical principles guiding ion flux, gradients, energetics, and selectivityInteractions and communication between ER and mitochondrial ion transport systemsMicrodomains and heterogeneity in organelle ion dynamicsRegulation of organelle ion transport by metabolic state, signaling networks, or membrane potentialStructural and kinetic analysis of organelle ion transporters and channelsQuantitative imaging, genetically encoded sensors, and advanced electrophysiological techniques for studying ion transportComputational modeling, data-driven inference, and AI-augmented approaches to mechanism and flux dynamicsImplications of disrupted organelle ion homeostasis for disease and therapeutic strategiesWe invite the submission of original research articles, methods papers, reviews, perspectives, and interdisciplinary studies that advance the molecular and quantitative understanding of ion transport in the ER and mitochondria, and illuminate its physiological and pathological relevance. Topic editors: Neelanjan Vishnu, Tarek Mohamed Abd El-Aziz, Ashutosh Kumar, Shankara Narayanan Varadarajan Source: https://www.frontiersin.org/research-topics/77481/organelle-ion-transport-in-the-endoplasmic-reticulum-and-mitochondria-biophysical-mechanisms-regulation-and-disease