Mitophagy and Mitochondrial Quality Control in Brain Aging and Neurodegeneration

Mitochondria are central to neuronal survival, synaptic function, and brain resilience across the lifespan. As the brain ages, mitochondrial dysfunction, impaired mitophagy, and defects in mitochondrial quality control pathways emerge as key drivers of neurodegeneration. Disrupted clearance of damaged mitochondria contributes to oxidative stress, energy failure, inflammation, and protein aggregation, all of which are hallmarks of disorders such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and other age-related cognitive and motor syndromes.

At the same time, brain aging is tightly linked to changes in innate and adaptive immunity, including microglial priming, altered astrocyte reactivity, neuroinflammation, and systemic “inflammaging.” Damaged or poorly cleared mitochondria can act as danger-associated molecular patterns (DAMPs), shaping microglial and astrocyte activation, peripheral immune responses, and blood–brain barrier integrity. Thus, mitophagy and mitochondrial quality control lie at the crossroads of neuronal health, glial function, and immune signaling in the aging brain.

This Research Topic aims to bring together mechanistic, translational, and clinical studies that clarify how mitophagy and mitochondrial quality control shape brain aging, neuroimmune interactions, and susceptibility to neurodegenerative disease. We welcome contributions that use diverse approaches – from molecular and cellular biology to immunology, systems neuroscience, omics, imaging, and computational modeling – to dissect how neurons and glial cells detect, repair, recycle, or eliminate dysfunctional mitochondria over time, and how these processes intersect with immune pathways in the central nervous system and periphery.

We particularly encourage submissions that:

1. Define molecular pathways and regulators of mitophagy and mitochondrial turnover in neurons, astrocytes, microglia, oligodendrocytes, and other brain-resident or infiltrating immune cells.
2. Explore how aging alters mitochondrial dynamics (fission, fusion, transport), biogenesis, and quality control in the central nervous system, and how these changes influence neuroinflammation and immune surveillance.
3. Link impaired mitophagy and mitochondrial dysfunction to specific neurodegenerative diseases, including genetic and sporadic forms, with a focus on neuroimmune mechanisms (e.g., microglial activation states, astrocyte reactivity, peripheral immune contributions).
4. Identify biomarkers of mitochondrial dysfunction, mitophagy, or mitochondrial-derived DAMPs in aging brains and in patients with neurodegenerative disorders, including immune or inflammatory signatures.
5. Use in vitro, in vivo, or organoid/humanized models to test how modulation of mitophagy or mitochondrial quality control impacts synaptic integrity, neuronal survival, glial phenotypes, neuroinflammation, cognition, or behavior.
6. Develop or evaluate therapeutic strategies – such as small molecules, gene therapies, biologics, cell-based therapies, or lifestyle interventions – that target mitochondrial quality control pathways and/or their crosstalk with immune and inflammatory signaling in the brain.
7. Apply single-cell, spatial, or multi-omics approaches to map mitochondrial heterogeneity, mitophagy activity, and associated immune states across brain cell types and regions during aging and in neurodegeneration.

By integrating work across mitochondrial biology, neuroimmunology, cellular phenotypes, and disease models, this Research Topic aims to advance our understanding of how mitochondrial quality control and immune signaling jointly shape healthy brain aging and neurodegeneration, and to identify new targets for preventing or slowing disease progression.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Mitophagy, Mitochondrial quality control, Brain aging, Neurodegeneration, Neuronal mitochondrial dysfunction

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.