Metabolic remodeling and mitochondrial dysfunction in regulated cell death and chronic disease

Chronic disease research increasingly points to the centrality of metabolic remodeling and mitochondrial dysfunction in dictating disease onset, severity, and progression. Persistent cellular stress leads to adaptations in energy production, redox balance, and biosynthetic pathways, all of which impact cellular survival and death mechanisms. Recent investigations have revealed how chronic disturbances in nutrient sensing, mitochondrial quality control, and organelle communication cultivate cellular environments conducive to maladaptive responses such as apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. Despite significant progress, critical questions remain about the precise causal relationships and the bidirectional interplay between stress-adaptive pathways and regulated cell death in chronic diseases - including cancer, neurodegeneration, cardiovascular, metabolic disorders, and tissue fibrosis.The latest evidence draws attention to the complexity of mitochondrial roles beyond bioenergetics, highlighting their influence on immunometabolism, proteostasis, mitophagy, and genome maintenance. Advanced techniques, such as metabolomics, single-cell analyses, and in vivo models, have driven discoveries in mitochondrial signaling and metabolic-immune crosstalk. However, much remains to be understood about how these integrated pathways converge to promote, restrain, or redirect cell death programs in human disease. Dissecting these networks presents an opportunity to identify reliable biomarkers and uncover therapeutic vulnerabilities that could be exploited using targeted interventions for diverse chronic conditions.This Research Topic aims to connect emerging mechanistic and translational insights in mitochondrial dysfunction, metabolic remodeling, and cell death regulation. By fostering research that clarifies molecular connections between metabolic stress and regulated cell death, the goal is to elucidate how these processes drive chronic pathology and uncover actionable targets for therapy.This Research Topic is restricted to studies that probe the intersection of metabolism, mitochondrial biology, and cell death programs primarily within the context of chronic diseases. We invite comprehensive work employing experimental, computational, and translational approaches. To gather further insights in this field, we welcome articles addressing, but not limited to, the following themes:Nutrient sensing and redox imbalance in chronic disease statesCalcium and lipid metabolism influencing regulated cell deathMitochondrial dynamics, quality control, and organelle crosstalkImmunometabolism and mitochondrial proteostasis (including UPRmt)Mitophagy, mitochondrial DNA damage signaling, and repair mechanismsMetabolic and mitochondrial regulation of inflammation and tissue remodelingMechanistic studies using metabolomics, single-cell profiling, and in vivo modelsIdentification of biomarkers and therapeutic targets for chronic diseasesSuitable article types include original research, reviews, mini-reviews, perspectives, and methods papers. Topic editors: Deokho Lee, Paola Maycotte Source: https://www.frontiersin.org/research-topics/78224/metabolic-remodeling-and-mitochondrial-dysfunction-in-regulated-cell-death-and-chronic-disease