ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
Evidence for Compartmentalized Axonal Mitochondrial Biogenesis: Mitochondrial DNA Replication Increases in Distal Axons As an Early Response to Parkinson's Disease-Relevant Stress.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Retrograde mitochondrial transport is required for mitochondrial biogenesis in zebrafish neurons.Nature communications · 2026Article
- Light-evoked activity and BDNF regulate mitochondrial dynamics and mitochondrial localized translation in CNS axons.iScience · 2025Article
- Retrograde mitochondrial transport regulates mitochondrial biogenesis in zebrafish neurons.bioRxiv : the preprint server for biology · 2025Article
- Imaging Mitochondrial Axonal Transport in Human Induced Pluripotent Stem Cell-Derived Neurons.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Aberrant mitochondrial DNA synthesis in macrophages exacerbates inflammation and atherosclerosis.Nature communications · 2024Article
- Axonal mitophagy in retinal ganglion cells.Cell communication and signaling : CCS · 2024Review
- Local mitochondrial replication in the periphery of neurons requires the eEF1A1 protein and thetranslation of nuclear-encoded proteins.iScience · 2024Article
- Neuropathogenesis-on-chips for neurodegenerative diseases.Nature communications · 2024Review
- The Role of PGC-1α-Mediated Mitochondrial Biogenesis in Neurons.Neurochemical research · 2023Review
- Mitochondrial regulation of local supply of energy in neurons.Current opinion in neurobiology · 2023Review
- How Organ-on-a-Chip Technology Can Assist in Studying the Role of the Glymphatic System in Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Understanding the Involvement of microRNAs in Mitochondrial Dysfunction and Their Role as Potential Biomarkers and Therapeutic Targets in Parkinson's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- How neurons maintain their axons long-term: an integrated view of axon biology and pathology.Frontiers in neuroscience · 2023Review
- Global Trends in Research of Mitochondrial Biogenesis over past 20 Years: A Bibliometric Analysis.Oxidative medicine and cellular longevity · 2023Article
- The Therapeutic Potential of Mitochondria Transplantation Therapy in Neurodegenerative and Neurovascular Disorders.Current neuropharmacology · 2023Review
- Programming axonal mitochondrial maintenance and bioenergetics in neurodegeneration and regeneration.Neuron · 2022Review
- Synapses: The Brain's Energy-Demanding Sites.International journal of molecular sciences · 2022Review
- Mitochondrial DNA Transport in Drosophila Neurons.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Energy matters: presynaptic metabolism and the maintenance of synaptic transmission.Nature reviews. Neuroscience · 2022Review
- Mitochondrial Biogenesis in Neurons: How and Where.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 3 countries.
Funding
Abstract
Dysregulation of mitochondrial biogenesis is implicated in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). However, it is not clear how mitochondrial biogenesis is regulated in neurons, with their unique compartmentalized anatomy and energetic demands. This is particularly relevant in PD because selectively vulnerable neurons feature long, highly arborized axons where degeneration initiates. We previously found that exposure of neurons to chronic, sublethal doses of rotenone, a complex I inhibitor linked to PD, causes early increases in mitochondrial density specifically in distal axons, suggesting possible upregulation of mitochondrial biogenesis within axons. Here, we directly evaluated for evidence of mitochondrial biogenesis in distal axons and examined whether PD-relevant stress causes compartmentalized alterations. Using BrdU labeling and imaging to quantify replicating mitochondrial DNA (mtDNA) in primary rat neurons (pooled from both sexes), we provide evidence of mtDNA replication in axons along with cell bodies and proximal dendrites. We found that exposure to chronic, sublethal rotenone increases mtDNA replication first in neurites and later extending to cell bodies, complementing our mitochondrial density data. Further, isolating axons from cell bodies and dendrites, we discovered that rotenone exposure upregulates mtDNA replication in distal axons. Utilizing superresolution stimulated emission depletion (STED) imaging, we identified mtDNA replication at sites of mitochondrial-endoplasmic reticulum contacts in axons. Our evidence suggests that mitochondrial biogenesis occurs not only in cell bodies, but also in distal axons, and is altered under PD-relevant stress conditions in an anatomically compartmentalized manner. We hypothesize that this contributes to vulnerability in neurodegenerative diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.