Deciphering the molecular signals of PINK1/Parkin mitophagy

Research output: Contribution to journalReview ArticleOtherpeer-review

127 Citations (Scopus)

Abstract

Functional mitochondria are critically important for the maintenance of cellular integrity and survival. Mitochondrial dysfunction is a major contributor to neurodegenerative diseases including Parkinson's disease (PD). Two gene products mutated in familial Parkinsonism, PINK1 and Parkin, function together to degrade damaged mitochondria through a selective form of autophagy termed mitophagy. PINK1 accumulates on the surface of dysfunctional mitochondria where it simultaneously recruits and activates Parkin's E3 ubiquitin ligase activity. This forms the basis of multiple signaling events that culminate in engulfment of damaged mitochondria within autophagosomes and degradation by lysosomes. This review discusses the molecular signals of PINK1/Parkin mitophagy and the ubiquitin code that drives not only Parkin recruitment and activation by PINK1 but also the downstream signaling events of mitophagy.
Original languageEnglish
Pages (from-to)733-744
Number of pages12
JournalTrends in Cell Biology
Volume26
Issue number10
DOIs
Publication statusPublished - Oct 2016

Keywords

  • Autophagy
  • Mitophagy
  • Parkin
  • Parkinson's disease
  • PINK1
  • ubiquitin

Cite this

@article{39d1b5e3ef3b4e5791ea62f1d1da2802,
title = "Deciphering the molecular signals of PINK1/Parkin mitophagy",
abstract = "Functional mitochondria are critically important for the maintenance of cellular integrity and survival. Mitochondrial dysfunction is a major contributor to neurodegenerative diseases including Parkinson's disease (PD). Two gene products mutated in familial Parkinsonism, PINK1 and Parkin, function together to degrade damaged mitochondria through a selective form of autophagy termed mitophagy. PINK1 accumulates on the surface of dysfunctional mitochondria where it simultaneously recruits and activates Parkin's E3 ubiquitin ligase activity. This forms the basis of multiple signaling events that culminate in engulfment of damaged mitochondria within autophagosomes and degradation by lysosomes. This review discusses the molecular signals of PINK1/Parkin mitophagy and the ubiquitin code that drives not only Parkin recruitment and activation by PINK1 but also the downstream signaling events of mitophagy.",
keywords = "Autophagy, Mitophagy, Parkin, Parkinson's disease, PINK1, ubiquitin",
author = "Nguyen, {Thanh N.} and Padman, {Benjamin S.} and Michael Lazarou",
year = "2016",
month = "10",
doi = "10.1016/j.tcb.2016.05.008",
language = "English",
volume = "26",
pages = "733--744",
journal = "Trends in Cell Biology",
issn = "0962-8924",
publisher = "Elsevier",
number = "10",

}

Deciphering the molecular signals of PINK1/Parkin mitophagy. / Nguyen, Thanh N.; Padman, Benjamin S.; Lazarou, Michael.

In: Trends in Cell Biology, Vol. 26, No. 10, 10.2016, p. 733-744.

Research output: Contribution to journalReview ArticleOtherpeer-review

TY - JOUR

T1 - Deciphering the molecular signals of PINK1/Parkin mitophagy

AU - Nguyen, Thanh N.

AU - Padman, Benjamin S.

AU - Lazarou, Michael

PY - 2016/10

Y1 - 2016/10

N2 - Functional mitochondria are critically important for the maintenance of cellular integrity and survival. Mitochondrial dysfunction is a major contributor to neurodegenerative diseases including Parkinson's disease (PD). Two gene products mutated in familial Parkinsonism, PINK1 and Parkin, function together to degrade damaged mitochondria through a selective form of autophagy termed mitophagy. PINK1 accumulates on the surface of dysfunctional mitochondria where it simultaneously recruits and activates Parkin's E3 ubiquitin ligase activity. This forms the basis of multiple signaling events that culminate in engulfment of damaged mitochondria within autophagosomes and degradation by lysosomes. This review discusses the molecular signals of PINK1/Parkin mitophagy and the ubiquitin code that drives not only Parkin recruitment and activation by PINK1 but also the downstream signaling events of mitophagy.

AB - Functional mitochondria are critically important for the maintenance of cellular integrity and survival. Mitochondrial dysfunction is a major contributor to neurodegenerative diseases including Parkinson's disease (PD). Two gene products mutated in familial Parkinsonism, PINK1 and Parkin, function together to degrade damaged mitochondria through a selective form of autophagy termed mitophagy. PINK1 accumulates on the surface of dysfunctional mitochondria where it simultaneously recruits and activates Parkin's E3 ubiquitin ligase activity. This forms the basis of multiple signaling events that culminate in engulfment of damaged mitochondria within autophagosomes and degradation by lysosomes. This review discusses the molecular signals of PINK1/Parkin mitophagy and the ubiquitin code that drives not only Parkin recruitment and activation by PINK1 but also the downstream signaling events of mitophagy.

KW - Autophagy

KW - Mitophagy

KW - Parkin

KW - Parkinson's disease

KW - PINK1

KW - ubiquitin

U2 - 10.1016/j.tcb.2016.05.008

DO - 10.1016/j.tcb.2016.05.008

M3 - Review Article

VL - 26

SP - 733

EP - 744

JO - Trends in Cell Biology

JF - Trends in Cell Biology

SN - 0962-8924

IS - 10

ER -