TY - JOUR
T1 - Transcellular degradation of axonal mitochondria
AU - Davis, Chung Ha O.
AU - Kim, Keun Young
AU - Bushong, Eric A.
AU - Mills, Elizabeth A.
AU - Boassa, Daniela
AU - Shih, Tiffany
AU - Kinebuchi, Mira
AU - Phan, Sebastien
AU - Zhou, Yi
AU - Bihlmeyer, Nathan A.
AU - Nguyen, Judy V.
AU - Jin, Yunju
AU - Ellisman, Mark H.
AU - Marsh-Armstrong, Nicholas
PY - 2014/7/1
Y1 - 2014/7/1
N2 - 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.
AB - 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.
KW - Mitophagy
KW - Phagocytosis
UR - http://www.scopus.com/inward/record.url?scp=84903694914&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903694914&partnerID=8YFLogxK
U2 - 10.1073/pnas.1404651111
DO - 10.1073/pnas.1404651111
M3 - Article
C2 - 24979790
AN - SCOPUS:84903694914
VL - 111
SP - 9633
EP - 9638
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 26
ER -