Transcellular degradation of axonal mitochondria

Chung Ha O. Davis, Keun Young Kim, Eric A. Bushong, Elizabeth A. Mills, Daniela Boassa, Tiffany Shih, Mira Kinebuchi, Sebastien Phan, Yi Zhou, Nathan A. Bihlmeyer, Judy V. Nguyen, Yunju Jin, Mark H. Ellisman, Nicholas Marsh-Armstrong

Research output: Contribution to journalArticle

208 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9633-9638
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number26
DOIs
StatePublished - Jul 1 2014
Externally publishedYes

Keywords

  • Mitophagy
  • Phagocytosis

ASJC Scopus subject areas

  • General

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