Mitochondrial Dysfunction and Redox Imbalance in Neurodegeneration: From Iron Homeostasis to Neuroinflammation and Oxidative Cell Death

Mitochondrial dysfunction is a converging feature of neurodegenerative disease, driving oxidative stress, disrupted redox and metal homeostasis, neuroinflammation and neuronal death. Two interconnected mechanisms are central to this process: dysregulation of iron metabolism, which promotes oxidative damage and ferroptotic vulnerability, and loss of mitochondrial redox control, which triggers neuroinflammation and apoptotic signaling cascades in neurons and glia. Emerging evidence points to a self-reinforcing cycle in which impaired mitochondrial function disrupts cellular iron handling, and in turn, iron accumulation and dysregulated ferritinophagy exacerbate mitochondrial oxidative damage — a cycle implicated across a broad spectrum of neurodegenerative and neuroinflammatory conditions.Despite substantial progress in characterizing these pathways individually, the mechanistic links between mitochondrial redox failure, iron dyshomeostasis, and downstream neuroinflammation and neuronal and glial death remain incompletely understood. Clarifying these connections is essential for identifying reliable biomarkers of disease progression and for developing therapies that intervene before irreversible cell loss occurs.This Research Topic welcomes studies addressing the cellular and molecular mechanisms linking mitochondrial dysfunction, oxidative/nitrosative stress, and iron dysregulation and neuroinflammation to neurodegeneration. We particularly encourage contributions on:• Mitochondrial oxidative stress and its role in neuronal and glial cell death (apoptotic and non-apoptotic pathways, including ferroptosis)• Iron dysregulation, ferritinophagy, and iron-mitochondria crosstalk in neurodegenerative disease• Glutathione and antioxidant defense systems in mitochondrial protection• Bcl-2 family and other regulators of mitochondrial integrity in neurodegeneration• Mitochondrial dysfunction and iron dyshomeostasis in neuroinflammation• Biomarkers of mitochondrial and redox dysfunction in neurodegenerative disease, including fluid and imaging markers• Therapeutic strategies targeting mitochondrial redox balance or iron homeostasis, from small molecules to metabolic and dietary interventionsWe welcome original research, reviews, and mini-reviews using in vitro, in vivo, or clinical/translational approaches across neurodegenerative conditions, including but not limited to Alzheimer’s disease, Parkinson’s disease, ALS, frontotemporal dementia, and other neurodegenerative and neuroinflammatory disorders. Studies bridging basic mechanistic work with translational or diagnostic applications are especially encouraged, as are contributions that integrate multiple disease models to test the generalizability of proposed mechanisms. Topic editors: Daniel Linseman, Isabella Zanella Source: https://www.frontiersin.org/research-topics/85714/mitochondrial-dysfunction-and-redox-imbalance-in-neurodegeneration-from-iron-homeostasis-to-neuroinflammation-and-oxidative-cell-death