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: To further examine the accumulation of Parkin on distal axonal mitochondria, we also used microfluidic devices with neurons transfected with mt-DsRed and YFP-Parkin. Depolarization of mitochondria with 40 ÂµM Antimycin A led to substantial recruitment of YFP-Parkin to axonal mitochondria (Fig. 6, A and B); within 20 min, the percentage of Parkin-positive mitochondria increased from 5 to 40% (P < 0.05; Fig. 6 E). In mock experiments in which the perfusion chamber did not contain Antimycin A, there was no increase in YFP-Parkinâ€“positive mitochondria (P = 0.2; Fig. 6 E).
Affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115.