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Mitochondrial dynamics and Parkinson's disease: focus on parkin.

Publication ,  Journal Article
Lim, K-L; Ng, X-H; Grace, LG-Y; Yao, T-P
Published in: Antioxid Redox Signal
May 1, 2012

SIGNIFICANCE: Parkinson's disease (PD) is a prevalent neurodegenerative disease affecting millions of individuals worldwide. Despite intensive efforts devoted to drug discovery, the disease remains incurable. To provide more effective medical therapy for PD, better understanding of the underlying causes of the disease is clearly necessary. RECENT ADVANCES: A broad range of studies conducted over the past few decades have collectively implicated aberrant mitochondrial homeostasis as a key contributor to the development of PD. Supporting this, mutations in several PD-linked genes are directly or indirectly linked to mitochondrial dysfunction. In particular, recent discoveries have identified parkin, whose mutations are causative of recessive parkinsonism, as a key regulator of mitochondrial homeostasis. CRITICAL ISSUES: Parkin appears to be involved in the entire spectrum of mitochondrial dynamics, including organelle biogenesis, fusion/fission, and clearance via mitophagy. How a single protein can regulate such diverse mitochondrial events is as intriguing as it is amazing; the mechanism underlying this is currently under intense research. Here, we provide an overview of mitochondrial dynamics and its relationship with neurodegenerative diseases and discuss current evidence and controversies surrounding the role of parkin in mitochondrial quality control and its relevance to PD pathogenesis. FUTURE DIRECTIONS: Although the emerging field of parkin-mediated mitochondrial quality control has proven to be exciting, it is important to recognize that PD pathogenesis is likely to involve an intricate network of interacting pathways. Elucidating the reciprocity of pathways, particularly how other PD-related pathways potentially influence mitochondrial homeostasis, may hold the key to therapeutic development.

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Published In

Antioxid Redox Signal

DOI

EISSN

1557-7716

Publication Date

May 1, 2012

Volume

16

Issue

9

Start / End Page

935 / 949

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Protein Ligases
  • Signal Transduction
  • Protein Kinases
  • Parkinson Disease
  • Mitochondria
  • Humans
  • Disease Models, Animal
  • Biochemistry & Molecular Biology
  • Autophagy
 

Citation

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Lim, K.-L., Ng, X.-H., Grace, L.-Y., & Yao, T.-P. (2012). Mitochondrial dynamics and Parkinson's disease: focus on parkin. Antioxid Redox Signal, 16(9), 935–949. https://doi.org/10.1089/ars.2011.4105
Lim, Kah-Leong, Xiao-Hui Ng, Lim Gui-Yin Grace, and Tso-Pang Yao. “Mitochondrial dynamics and Parkinson's disease: focus on parkin.Antioxid Redox Signal 16, no. 9 (May 1, 2012): 935–49. https://doi.org/10.1089/ars.2011.4105.
Lim K-L, Ng X-H, Grace LG-Y, Yao T-P. Mitochondrial dynamics and Parkinson's disease: focus on parkin. Antioxid Redox Signal. 2012 May 1;16(9):935–49.
Lim, Kah-Leong, et al. “Mitochondrial dynamics and Parkinson's disease: focus on parkin.Antioxid Redox Signal, vol. 16, no. 9, May 2012, pp. 935–49. Pubmed, doi:10.1089/ars.2011.4105.
Lim K-L, Ng X-H, Grace LG-Y, Yao T-P. Mitochondrial dynamics and Parkinson's disease: focus on parkin. Antioxid Redox Signal. 2012 May 1;16(9):935–949.
Journal cover image

Published In

Antioxid Redox Signal

DOI

EISSN

1557-7716

Publication Date

May 1, 2012

Volume

16

Issue

9

Start / End Page

935 / 949

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Protein Ligases
  • Signal Transduction
  • Protein Kinases
  • Parkinson Disease
  • Mitochondria
  • Humans
  • Disease Models, Animal
  • Biochemistry & Molecular Biology
  • Autophagy