Skip to main content

Convergence of Parkin, PINK1, and α-Synuclein on Stress-induced Mitochondrial Morphological Remodeling.

Publication ,  Journal Article
Norris, KL; Hao, R; Chen, L-F; Lai, C-H; Kapur, M; Shaughnessy, PJ; Chou, D; Yan, J; Taylor, JP; Engelender, S; West, AE; Lim, K-L; Yao, T-P
Published in: J Biol Chem
May 29, 2015

Mutations in PARKIN (PARK2), an ubiquitin ligase, cause early onset Parkinson disease. Parkin was shown to bind, ubiquitinate, and target depolarized mitochondria for destruction by autophagy. This process, mitophagy, is considered crucial for maintaining mitochondrial integrity and suppressing Parkinsonism. Here, we report that under moderate mitochondrial stress, parkin does not translocate to mitochondria to induce mitophagy; rather, it stimulates mitochondrial connectivity. Mitochondrial stress-induced fusion requires PINK1 (PARK6), mitofusins, and parkin ubiquitin ligase activity. Upon exposure to mitochondrial toxins, parkin binds α-synuclein (PARK1), and in conjunction with the ubiquitin-conjugating enzyme Ubc13, stimulates K63-linked ubiquitination. Importantly, α-synuclein inactivation phenocopies parkin overexpression and suppresses stress-induced mitochondria fission, whereas Ubc13 inactivation abrogates parkin-dependent mitochondrial fusion. The convergence of parkin, PINK1, and α-synuclein on mitochondrial dynamics uncovers a common function of these PARK genes in the mitochondrial stress response and provides a potential physiological basis for the prevalence of α-synuclein pathology in Parkinson disease.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

May 29, 2015

Volume

290

Issue

22

Start / End Page

13862 / 13874

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Ubiquitin-Protein Ligases
  • Ubiquitin
  • Protein Kinases
  • Phosphorylation
  • Parkinson Disease
  • Neurons
  • Mutation
  • Mitophagy
  • Mitochondria
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Norris, K. L., Hao, R., Chen, L.-F., Lai, C.-H., Kapur, M., Shaughnessy, P. J., … Yao, T.-P. (2015). Convergence of Parkin, PINK1, and α-Synuclein on Stress-induced Mitochondrial Morphological Remodeling. J Biol Chem, 290(22), 13862–13874. https://doi.org/10.1074/jbc.M114.634063
Norris, Kristi L., Rui Hao, Liang-Fu Chen, Chun-Hsiang Lai, Meghan Kapur, Peter J. Shaughnessy, Dennis Chou, et al. “Convergence of Parkin, PINK1, and α-Synuclein on Stress-induced Mitochondrial Morphological Remodeling.J Biol Chem 290, no. 22 (May 29, 2015): 13862–74. https://doi.org/10.1074/jbc.M114.634063.
Norris KL, Hao R, Chen L-F, Lai C-H, Kapur M, Shaughnessy PJ, et al. Convergence of Parkin, PINK1, and α-Synuclein on Stress-induced Mitochondrial Morphological Remodeling. J Biol Chem. 2015 May 29;290(22):13862–74.
Norris, Kristi L., et al. “Convergence of Parkin, PINK1, and α-Synuclein on Stress-induced Mitochondrial Morphological Remodeling.J Biol Chem, vol. 290, no. 22, May 2015, pp. 13862–74. Pubmed, doi:10.1074/jbc.M114.634063.
Norris KL, Hao R, Chen L-F, Lai C-H, Kapur M, Shaughnessy PJ, Chou D, Yan J, Taylor JP, Engelender S, West AE, Lim K-L, Yao T-P. Convergence of Parkin, PINK1, and α-Synuclein on Stress-induced Mitochondrial Morphological Remodeling. J Biol Chem. 2015 May 29;290(22):13862–13874.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

May 29, 2015

Volume

290

Issue

22

Start / End Page

13862 / 13874

Location

United States

Related Subject Headings

  • alpha-Synuclein
  • Ubiquitin-Protein Ligases
  • Ubiquitin
  • Protein Kinases
  • Phosphorylation
  • Parkinson Disease
  • Neurons
  • Mutation
  • Mitophagy
  • Mitochondria