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Transcellular degradation of axonal mitochondria
Open accessAbstract
Significance: Mitochondria are organelles that perform many essential functions, including providing the energy to cells. Cells remove damaged mitochondria through a process called mitophagy. Mitophagy is considered a subset of a process called autophagy, by which damaged organelles are enwrapped and delivered to lysosomes for degradation. Implicit in the categorization of mitophagy as a subset of autophagy, which means “self-eating,” is the assumption that a cell degrades its own mitochondria. However, we show here that in a location called the optic nerve head, large numbers of mitochondria are shed from neurons to be degraded by the lysosomes of adjoining glial cells. This finding calls into question the assumption that a cell necessarily degrades its own organelles.
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“Cells with mitochondrial defects might release the damaged mitochondria to be picked up by other cells, thereby facilitating their degradation by recipient cells279.”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [279]
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“Interestingly, degradation of neuronal mitochondria can occur in a non-cell autonomous fashion, as demonstrated by the astrocytic engulfment and degradation of mitochondria excreted from retinal ganglion cells [60].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [60]
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Metadata
- Authors
- Davis, C.-H. O., Kim, K.-Y., Bushong, E. A., Mills, E. A., Boassa, D., Shih, T., Kinebuchi, M., Phan, S., Zhou, Y., Bihlmeyer, N. A., Nguyen, J. V., Jin, Y., Ellisman, M. H., & Marsh-Armstrong, N.
- Affiliations
- Kennedy Krieger Institute (US)
- University of California San Diego (US)
- National Center for Microscopy and Imaging Research, Center for Research in Biological Systems, Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093
- Johns Hopkins University (US)
- The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-06-16
- Volume
- 111
- Issue
- 26
- Pages
- 9633-9638
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4084443
- OpenAlex
- W2025060864
- Cited by
- 673
- References
- 29
- Citations by year
- 2026: 48 · 2025: 72 · 2024: 66 · 2023: 84 · 2022: 65 · 2021: 72 · 2020: 61 · 2019: 48 · 2018: 38 · 2017: 52 · 2016: 30 · 2015: 28 · 2014: 8
- FWCI
- 29.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation (DGE-1,232,825, 1232825)
- Glaucoma Research Foundation
- Barr Foundation
- National Institutes of Health (5r01ey022680-02)
- National Institute on Drug Abuse (R01DA016602, DA016602)
- National Eye Institute (R01 EY022680, R01EY019960)
- National Institute of General Medical Sciences (R01GM082949, P41GM103412, T32GM007814, 5-T32-GM07814, 5R01GM82949)
- National Institute of Neurological Disorders and Stroke (P30NS050274)
- National Center for Research Resources (P41RR004050, DA016602)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- mitochondrial degradation, retinal ganglion cell axons, optic nerve head, astrocytes, axonal mitochondria, lysosomes, neuronal mitochondria
- MeSH terms
- Red Fluorescent Protein, Animals, Astrocytes, Axons, Exocytosis, Immunohistochemistry, Luminescent Proteins, Lysosomes, Optic Disk, Phagocytosis, Retinal Ganglion Cells, In Situ Hybridization, Fluorescence, In Situ Nick-End Labeling, Imaging, Three-Dimensional, Mice, Electron Microscope Tomography, Mitophagy
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