title: Transcellular degradation of axonal mitochondria.
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.
authors: The 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.
authors: Chung-ha O
authors: CH
authors: Davis
authors: 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.
authors: Keun-Young
authors: KY
authors: Kim
authors: 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.
authors: Eric A
authors: EA
authors: Bushong
authors: The 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.
authors: Elizabeth A
authors: EA
authors: Mills
authors: 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.
authors: Daniela
authors: D
authors: Boassa
authors: 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.
authors: Tiffany
authors: T
authors: Shih
authors: 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.
authors: Mira
authors: M
authors: Kinebuchi
authors: 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.
authors: Sebastien
authors: S
authors: Phan
authors: Hugo W. Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD 21205; and.
authors: Yi
authors: Y
authors: Zhou
authors: Hugo W. Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD 21205; and.
authors: Nathan A
authors: NA
authors: Bihlmeyer
authors: The 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.
authors: Judy V
authors: JV
authors: Nguyen
authors: The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors: Yunju
authors: Y
authors: Jin
authors: 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.
authors: Mark H
authors: MH
authors: Ellisman
authors: The 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 marsh-armstrong@jhmi.edu.
authors: Nicholas
authors: N
authors: Marsh-Armstrong
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001369:Axons / Q000502:physiology*; D055032:Electron Microscope Tomography; D005089:Exocytosis / Q000502:physiology; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020287:In Situ Nick-End Labeling; D008164:Luminescent Proteins; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D063306:Mitophagy / Q000502:physiology*; D009898:Optic Disk / Q000166:cytology*; D010587:Phagocytosis / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D000097573:Red Fluorescent Protein
chemical_list: D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein
keywords: mitophagy; phagocytosis