Regulation of PINK1-Parkin-mediated mitophagy

Wolfdieter Springer, Philipp J. Kahle

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Parkinson disease (PD) is a devastating disorder of the nervous system for which no cure exists. Although the exact mechanisms involved in the pathogenesis of PD are unclear, very recently, a novel cellular process has been identified that promises great future potential. Two PD-associated genes have been found to converge on the emerging mitophagy pathway that links the two major cellular dysfunctions implicated in the pathogenesis of PD. Thereby, PINK1 and Parkin physically associate and functionally cooperate to identify and label damaged mitochondria for selective degradation via autophagy. PD-associated mutations in both genes disrupt mitophagy although through different mechanisms, revealing a sequential multistep process. Further key players that tie into this process have been identified and provide the framework for future research aiming at a complete dissection of this neuroprotective pathway. This may not only yield novel targets for therapeutic intervention in PD, but possibly for other neurodegenerative disorders as well.

Original languageEnglish (US)
Pages (from-to)266-278
Number of pages13
JournalAutophagy
Volume7
Issue number3
DOIs
StatePublished - Mar 2011
Externally publishedYes

Fingerprint

Mitochondrial Degradation
Parkinson Disease
Autophagy
Nervous System Diseases
Neurodegenerative Diseases
Genes
Dissection
Mitochondria
Mutation

Keywords

  • Autophagy
  • HDAC6
  • Mitochondria
  • Mitofusin
  • p62/SQSTM1
  • Parkin
  • Parkinson disease
  • PINK1
  • Ubiquitin
  • VDAC1

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Regulation of PINK1-Parkin-mediated mitophagy. / Springer, Wolfdieter; Kahle, Philipp J.

In: Autophagy, Vol. 7, No. 3, 03.2011, p. 266-278.

Research output: Contribution to journalArticle

Springer, Wolfdieter ; Kahle, Philipp J. / Regulation of PINK1-Parkin-mediated mitophagy. In: Autophagy. 2011 ; Vol. 7, No. 3. pp. 266-278.
@article{b00df353bd0f4354ac1f2b897c068136,
title = "Regulation of PINK1-Parkin-mediated mitophagy",
abstract = "Parkinson disease (PD) is a devastating disorder of the nervous system for which no cure exists. Although the exact mechanisms involved in the pathogenesis of PD are unclear, very recently, a novel cellular process has been identified that promises great future potential. Two PD-associated genes have been found to converge on the emerging mitophagy pathway that links the two major cellular dysfunctions implicated in the pathogenesis of PD. Thereby, PINK1 and Parkin physically associate and functionally cooperate to identify and label damaged mitochondria for selective degradation via autophagy. PD-associated mutations in both genes disrupt mitophagy although through different mechanisms, revealing a sequential multistep process. Further key players that tie into this process have been identified and provide the framework for future research aiming at a complete dissection of this neuroprotective pathway. This may not only yield novel targets for therapeutic intervention in PD, but possibly for other neurodegenerative disorders as well.",
keywords = "Autophagy, HDAC6, Mitochondria, Mitofusin, p62/SQSTM1, Parkin, Parkinson disease, PINK1, Ubiquitin, VDAC1",
author = "Wolfdieter Springer and Kahle, {Philipp J.}",
year = "2011",
month = "3",
doi = "10.4161/auto.7.3.14348",
language = "English (US)",
volume = "7",
pages = "266--278",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "3",

}

TY - JOUR

T1 - Regulation of PINK1-Parkin-mediated mitophagy

AU - Springer, Wolfdieter

AU - Kahle, Philipp J.

PY - 2011/3

Y1 - 2011/3

N2 - Parkinson disease (PD) is a devastating disorder of the nervous system for which no cure exists. Although the exact mechanisms involved in the pathogenesis of PD are unclear, very recently, a novel cellular process has been identified that promises great future potential. Two PD-associated genes have been found to converge on the emerging mitophagy pathway that links the two major cellular dysfunctions implicated in the pathogenesis of PD. Thereby, PINK1 and Parkin physically associate and functionally cooperate to identify and label damaged mitochondria for selective degradation via autophagy. PD-associated mutations in both genes disrupt mitophagy although through different mechanisms, revealing a sequential multistep process. Further key players that tie into this process have been identified and provide the framework for future research aiming at a complete dissection of this neuroprotective pathway. This may not only yield novel targets for therapeutic intervention in PD, but possibly for other neurodegenerative disorders as well.

AB - Parkinson disease (PD) is a devastating disorder of the nervous system for which no cure exists. Although the exact mechanisms involved in the pathogenesis of PD are unclear, very recently, a novel cellular process has been identified that promises great future potential. Two PD-associated genes have been found to converge on the emerging mitophagy pathway that links the two major cellular dysfunctions implicated in the pathogenesis of PD. Thereby, PINK1 and Parkin physically associate and functionally cooperate to identify and label damaged mitochondria for selective degradation via autophagy. PD-associated mutations in both genes disrupt mitophagy although through different mechanisms, revealing a sequential multistep process. Further key players that tie into this process have been identified and provide the framework for future research aiming at a complete dissection of this neuroprotective pathway. This may not only yield novel targets for therapeutic intervention in PD, but possibly for other neurodegenerative disorders as well.

KW - Autophagy

KW - HDAC6

KW - Mitochondria

KW - Mitofusin

KW - p62/SQSTM1

KW - Parkin

KW - Parkinson disease

KW - PINK1

KW - Ubiquitin

KW - VDAC1

UR - http://www.scopus.com/inward/record.url?scp=79952324644&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952324644&partnerID=8YFLogxK

U2 - 10.4161/auto.7.3.14348

DO - 10.4161/auto.7.3.14348

M3 - Article

VL - 7

SP - 266

EP - 278

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 3

ER -