Skip to main content

Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons.

Publication ,  Journal Article
Evans, CS; Holzbaur, EL
Published in: Elife
January 14, 2020

Mitophagy, the selective removal of damaged mitochondria, is thought to be critical to maintain neuronal homeostasis. Mutations of proteins in the pathway cause neurodegenerative diseases, suggesting defective mitochondrial turnover contributes to neurodegeneration. In primary rat hippocampal neurons, we developed a mitophagy induction paradigm where mild oxidative stress induced low levels of mitochondrial damage. Mitophagy-associated proteins were sequentially recruited to depolarized mitochondria followed by sequestration into autophagosomes. The localization of these mitophagy events had a robust somal bias. In basal and induced conditions, engulfed mitochondria remained in non-acidified organelles for hours to days, illustrating efficient autophagosome sequestration but delayed lysosomal fusion or acidification. Furthermore, expression of an ALS-linked mutation in the pathway disrupted mitochondrial network integrity and this effect was exacerbated by oxidative stress. Thus, age-related decline in neuronal health or expression of disease-associated mutations in the pathway may exacerbate the slow kinetics of neuronal mitophagy, leading to neurodegeneration.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

January 14, 2020

Volume

9

Location

England

Related Subject Headings

  • Transcription Factor TFIIIA
  • Reactive Oxygen Species
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Small Interfering
  • Protein Kinases
  • Phagosomes
  • Oxidative Stress
  • Neurons
  • Neurodegenerative Diseases
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Evans, C. S., & Holzbaur, E. L. (2020). Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons. Elife, 9. https://doi.org/10.7554/eLife.50260
Evans, Chantell S., and Erika Lf Holzbaur. “Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons.Elife 9 (January 14, 2020). https://doi.org/10.7554/eLife.50260.
Evans, Chantell S., and Erika Lf Holzbaur. “Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons.Elife, vol. 9, Jan. 2020. Pubmed, doi:10.7554/eLife.50260.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

January 14, 2020

Volume

9

Location

England

Related Subject Headings

  • Transcription Factor TFIIIA
  • Reactive Oxygen Species
  • Rats, Sprague-Dawley
  • Rats
  • RNA, Small Interfering
  • Protein Kinases
  • Phagosomes
  • Oxidative Stress
  • Neurons
  • Neurodegenerative Diseases