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Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin.

Ashrafi G, Schlehe JS, LaVoie MJ, Schwarz TL - J. Cell Biol. (2014)

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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 F.M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, MA 02115.

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Parkin recruitment by Antimycin A and Veratridine. (A–D) Exposing axonal segments to 40 µM Antimycin A (Ant A; A and B) or 250 nM Veratridine (C and D) led to recruitment of YFP-Parkin to mitochondria (cyan arrowheads). Orange and brown arrowheads denote corresponding points in images and line scans. (E) Frequency of YFP-Parkin recruitment. n = 59–98 mitochondria from four microfluidic devices per condition. *, P < 0.05. Error bars represent means ± SEM. AU, arbitrary unit. Bars, 5 µm.
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fig6: Parkin recruitment by Antimycin A and Veratridine. (A–D) Exposing axonal segments to 40 µM Antimycin A (Ant A; A and B) or 250 nM Veratridine (C and D) led to recruitment of YFP-Parkin to mitochondria (cyan arrowheads). Orange and brown arrowheads denote corresponding points in images and line scans. (E) Frequency of YFP-Parkin recruitment. n = 59–98 mitochondria from four microfluidic devices per condition. *, P < 0.05. Error bars represent means ± SEM. AU, arbitrary unit. Bars, 5 µm.

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 µM 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-Parkin–positive mitochondria (P = 0.2; Fig. 6 E).


Mitophagy of damaged mitochondria occurs locally in distal neuronal axons and requires PINK1 and Parkin.

Ashrafi G, Schlehe JS, LaVoie MJ, Schwarz TL - J. Cell Biol. (2014)

Parkin recruitment by Antimycin A and Veratridine. (A–D) Exposing axonal segments to 40 µM Antimycin A (Ant A; A and B) or 250 nM Veratridine (C and D) led to recruitment of YFP-Parkin to mitochondria (cyan arrowheads). Orange and brown arrowheads denote corresponding points in images and line scans. (E) Frequency of YFP-Parkin recruitment. n = 59–98 mitochondria from four microfluidic devices per condition. *, P < 0.05. Error bars represent means ± SEM. AU, arbitrary unit. Bars, 5 µm.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4151150&req=5

fig6: Parkin recruitment by Antimycin A and Veratridine. (A–D) Exposing axonal segments to 40 µM Antimycin A (Ant A; A and B) or 250 nM Veratridine (C and D) led to recruitment of YFP-Parkin to mitochondria (cyan arrowheads). Orange and brown arrowheads denote corresponding points in images and line scans. (E) Frequency of YFP-Parkin recruitment. n = 59–98 mitochondria from four microfluidic devices per condition. *, P < 0.05. Error bars represent means ± SEM. AU, arbitrary unit. Bars, 5 µm.
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 µM 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-Parkin–positive mitochondria (P = 0.2; Fig. 6 E).

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.

View Article: PubMed Central - HTML - PubMed

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
Related in: MedlinePlus