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Updated: Apr 27, 2026
Morphological and Functional Evaluation of Axons and their Synapses during Axon Death in Drosophila melanogaster
Published on: March 16, 2020
Transcellular degradation of axonal mitochondria
Chung-ha O Davis1, Keun-Young Kim2, Eric A Bushong2
1The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;Hugo W. Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD 21205; and.
Abstract:
It is generally accepted that healthy cells degrade their own mitochondria. Here, we report that retinal ganglion cell axons of WT mice shed mitochondria at the optic nerve head (ONH), and that these mitochondria are internalized and degraded by adjacent astrocytes. EM demonstrates that mitochondria are shed through formation of large protrusions that originate from otherwise healthy axons. A virally introduced tandem fluorophore protein reporter of acidified mitochondria reveals that acidified axonal mitochondria originating from the retinal ganglion cell are associated with lysosomes within columns of astrocytes in the ONH. According to this reporter, a greater proportion of retinal ganglion cell mitochondria are degraded at the ONH than in the ganglion cell soma. Consistently, analyses of degrading DNA reveal extensive mtDNA degradation within the optic nerve astrocytes, some of which comes from retinal ganglion cell axons. Together, these results demonstrate that surprisingly large proportions of retinal ganglion cell axonal mitochondria are normally degraded by the astrocytes of the ONH. This transcellular degradation of mitochondria, or transmitophagy, likely occurs elsewhere in the CNS, because structurally similar accumulations of degrading mitochondria are also found along neurites in superficial layers of the cerebral cortex. Thus, the general assumption that neurons or other cells necessarily degrade their own mitochondria should be reconsidered.
Insights
Healthy neurons shed mitochondria, which are then degraded by neighboring astrocytes at the optic nerve head. This newly discovered process, transmitophagy, challenges the assumption that cells only degrade their own mitochondria.
Area of Science:
- Neuroscience
- Cell Biology
- Mitochondrial Biology
Background:
- Cells typically degrade their own mitochondria through mitophagy.
- The fate of mitochondria in neuronal axons, particularly at the optic nerve head (ONH), remains incompletely understood.
Purpose of the Study:
- To investigate the degradation process of mitochondria in retinal ganglion cell axons.
- To determine if transcellular degradation of mitochondria occurs in the central nervous system (CNS).
Main Methods:
- Utilized wild-type (WT) mice.
- Employed electron microscopy (EM) for ultrastructural analysis.
- Used a virally introduced tandem fluorophore protein reporter for acidified mitochondria.
- Analyzed degrading DNA (mtDNA) within optic nerve astrocytes.
Main Results:
- Retinal ganglion cell axons shed mitochondria at the ONH via large protrusions.
- Adjacent astrocytes internalize and degrade these shed axonal mitochondria.
- A greater proportion of retinal ganglion cell mitochondria are degraded at the ONH compared to the ganglion cell soma.
- Evidence of mtDNA degradation within optic nerve astrocytes, originating from retinal ganglion cell axons.
- Similar mitochondrial degradation observed along neurites in the cerebral cortex, suggesting a broader phenomenon.
Conclusions:
- A significant portion of retinal ganglion cell axonal mitochondria are degraded by optic nerve head astrocytes.
- Introduced the concept of transmitophagy: the transcellular degradation of mitochondria.
- This process challenges the established view of mitochondrial degradation being solely an intracellular event.
- Transmitophagy likely occurs in other areas of the CNS, indicating a fundamental mechanism for mitochondrial quality control in neurons.
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