Top

Minireview

Split Viewer

Mol. Cells 2012; 34(1): 7-13

Published online July 31, 2012

https://doi.org/10.1007/s10059-012-0100-8

© The Korean Society for Molecular and Cellular Biology

PINK1 as a Molecular Checkpoint in the Maintenance of Mitochondrial Function and Integrity

Hyongjong Koh1,*, and Jongkyeong Chung2,*

1Department of Pharmacology, Mitochondria Hub Regulation Center (MHRC), Dong-A University College of Medicine, Busan 602-714, Korea, 2School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea

Correspondence to : *Correspondence: hjkoh@dau.ac.kr (HK); jkc@snu.ac.kr (JC)

Received: April 6, 2012; Accepted: April 24, 2012

Abstract

Parkinson’s disease (PD), the most prevalent neurodegenerative movement disorder, is characterized by an age-dependent selective loss of dopaminergic (DA) neurons. Although most PD cases are sporadic, more than 20 responsible genes in familial cases were identified recently. Genetic studies using Drosophila models demonstrate that PINK1, a mitochondrial kinase encoded by a PD-linked gene PINK1, is critical for maintaining mitochondrial function and integrity. This suggests that mitochondrial dysfunction is the main cause of PD pathogenesis. Further genetic and cell biological studies revealed that PINK1 recruits Parkin, an E3 ubiquitin ligase encoded by another PD-linked gene parkin, to mitochondria and regulates the mitochondrial remodeling process via the Parkin-mediated ubiquitination of various mitochondrial proteins. PINK1 also directly phosphorylates the mitochondrial proteins Miro and TRAP1, subsequently inhibiting mitochondrial transport and mitochondrial oxidative damage, respectively. Moreover, recent Drosophila genetic analyses demonstrate that the neuroprotective molecules Sir2 and FOXO specifically complement mito-chondrial dysfunction and DA neuron loss in PINK1 null mutants, suggesting that Sir2 and FOXO protect mitochondria and DA neurons downstream of PINK1. Collectively, these recent results suggest that PINK1 plays multiple roles in mitochondrial quality control by regulating its mitochondrial, cytosolic, and nuclear targets.

Keywords FOXO, Drosophila, mitochondrial dysfunction, Parkin, Parkinson’s disease, PINK1, Sir2

Article

Minireview

Mol. Cells 2012; 34(1): 7-13

Published online July 31, 2012 https://doi.org/10.1007/s10059-012-0100-8

Copyright © The Korean Society for Molecular and Cellular Biology.

PINK1 as a Molecular Checkpoint in the Maintenance of Mitochondrial Function and Integrity

Hyongjong Koh1,*, and Jongkyeong Chung2,*

1Department of Pharmacology, Mitochondria Hub Regulation Center (MHRC), Dong-A University College of Medicine, Busan 602-714, Korea, 2School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea

Correspondence to:*Correspondence: hjkoh@dau.ac.kr (HK); jkc@snu.ac.kr (JC)

Received: April 6, 2012; Accepted: April 24, 2012

Abstract

Parkinson’s disease (PD), the most prevalent neurodegenerative movement disorder, is characterized by an age-dependent selective loss of dopaminergic (DA) neurons. Although most PD cases are sporadic, more than 20 responsible genes in familial cases were identified recently. Genetic studies using Drosophila models demonstrate that PINK1, a mitochondrial kinase encoded by a PD-linked gene PINK1, is critical for maintaining mitochondrial function and integrity. This suggests that mitochondrial dysfunction is the main cause of PD pathogenesis. Further genetic and cell biological studies revealed that PINK1 recruits Parkin, an E3 ubiquitin ligase encoded by another PD-linked gene parkin, to mitochondria and regulates the mitochondrial remodeling process via the Parkin-mediated ubiquitination of various mitochondrial proteins. PINK1 also directly phosphorylates the mitochondrial proteins Miro and TRAP1, subsequently inhibiting mitochondrial transport and mitochondrial oxidative damage, respectively. Moreover, recent Drosophila genetic analyses demonstrate that the neuroprotective molecules Sir2 and FOXO specifically complement mito-chondrial dysfunction and DA neuron loss in PINK1 null mutants, suggesting that Sir2 and FOXO protect mitochondria and DA neurons downstream of PINK1. Collectively, these recent results suggest that PINK1 plays multiple roles in mitochondrial quality control by regulating its mitochondrial, cytosolic, and nuclear targets.

Keywords: FOXO, Drosophila, mitochondrial dysfunction, Parkin, Parkinson’s disease, PINK1, Sir2

Mol. Cells
May 31, 2022 Vol.45 No.5, pp. 273~352
COVER PICTURE
Fe2+ ion depletion-induced expression of BΔGFP at the early stage of leaf development (Choi et al., pp. 294-305).

Share this article on

  • line
  • mail

Related articles in Mol. Cells

Molecules and Cells

eISSN 0219-1032
qr-code Download