Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin.
Bottom Line: In PINK1(-/-) axons, damaged mitochondria did not accumulate Parkin and failed to be engulfed in autophagosomes.Similarly, initiation of mitophagy was blocked in Parkin(-/-) axons.Local mitophagy likely provides rapid neuroprotection against oxidative stress without a requirement for retrograde transport to the soma.
Affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115.Show MeSH
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Mentions: Although mt-KR can restrict damage to a few mitochondria, quantitative examination of mitophagy required damage to a larger population of axonal mitochondria, while still sparing the majority of mitochondria in a neuron. To this end, we took advantage of microfluidic local perfusion chambers (Taylor et al., 2010). Fluidic isolation of compartments in these devices allows for the selective pharmacological manipulation of a subset of axonal mitochondria. Hippocampal neurons were plated in the somal compartment and extended axons through two sets of 200-µm-long microgrooves that were separated by a 100-µm-long perfusion chamber (Fig. 2 A).
Affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115.