Cellular stressors have been demonstrated to exert a substantial influence on the functionality of organelles, thereby impacting cellular homeostasis and contributing to the development of disease pathogenesis. This review aims to examine the impact of diverse stressors, including environmental, chemical, biological, and physical factors, on critical organelles such as the cell membrane, mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomes, and membrane-less organelles. The intricate molecular mechanisms underlying cellular stress responses, encompassing oxidative stress, protein misfolding, and metabolic reprogramming, have the capacity to elicit adaptive responses or culminate in pathological conditions. The interplay between these stressors and organelle dysfunction has been implicated in a myriad of diseases, including neurodegenerative disorders, cancer, metabolic disorders, and immune-related pathologies. A comprehensive understanding of the mechanisms by which organelles respond to stress can offer valuable insights into the development of therapeutic strategies aimed at mitigating cellular damage.

Cancer remains a major global health burden driven by genetic, metabolic, and microenvironmental alterations. Although reactive oxygen species (ROS) and oxidative stress have long been implicated in cancer biology, current understanding remains fragmented and, in several areas, conceptually disputed considering how ROS and oxidative stress thresholds determine the switch between tumor-promoting signaling and cytotoxic outcomes, and whether redox-based therapies can be safely and selectively applied across different cancer types. Moreover, existing studies often examine isolated pathways or single ROS, leaving unanswered the question of how spatial and temporal ROS dynamics and oxidative stress responses shape carcinogenesis, metastasis, and therapeutic resistance. This review moves beyond descriptive summarization by critically examining unresolved mechanistic gaps, including (i) how ROS and oxidative stress interact with epigenetic and metabolic reprogramming, (ii) the context-dependent role of ROS-driven oxidative stress within the tumor microenvironment and immune evasion, and (iii) why ROS-targeting and oxidative stress-modulating therapies have shown inconsistent clinical translation despite promising preclinical data. We highlight areas of consensus as well as conflicting evidence, synthesizing recent advances across multiple cancer types to clarify where ROS and oxidative stress function as drivers, modulators, or vulnerabilities. Finally, we outline emerging research priorities, such as real-time redox profiling, subtype-specific targeting strategies, and combination approaches, to guide the development of more precise and effective ROS- and oxidative-stress-based interventions.

In the last twenty years, an increasing volume of research has characterized lipids as dynamic signaling molecules that play essential roles in various physiological and pathological processes, especially concerning chronic diseases such as cardiovascular disorders, diabetes, liver disease, neurodegeneration, cancer, obesity, diabetic and chronic kidney diseases and atherosclerosis. Dysregulation of lipid synthesis and storage, lipolysis, fatty acid oxidation, lipid signaling pathways, and organelle-specific lipid modifications, including mitochondrial phospholipid remodeling and endoplasmic reticulum stress induced by saturated fatty acids, are recognized as contributors to the initiation and progression of this pathogenesis. Concurrently with the increasing comprehension of lipid metabolism, the last decade has seen progress in the understanding of genome control, especially with non-coding RNAs (ncRNAs). MicroRNAs, long non-coding RNAs, and circular RNAs, as ncRNAs, are essential modulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels that affect a number of lipid metabolism-related processes, such as fatty acid synthesis and oxidation, cholesterol homeostasis, and lipid droplet dynamics. Therapeutically, ncRNAs hold considerable promise owing to their tissue specificity and modularity, with antisense oligonucleotides and CRISPR-based editing currently under preclinical evaluation. In this context, we review recent studies exploring the interplay between ncRNAs and the regulatory networks governing lipid metabolism, and how disruptions in these networks contribute to chronic disease. This emerging paradigm underscores the role of ncRNA–lipid metabolism interactions as central nodes in metabolic and inflammatory pathways, highlighting the need for a holistic approach to therapeutic targeting.