Transcellular degradation of axonal 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.