PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival
Mutations in PTEN-induced putative kinase 1 (PINK1) and parkin cause autosomal-recessive Parkinson’s disease through a common pathway involving mitochondrial quality control. Parkin inactivation leads to accumulation of the parkin interacting substrate (PARIS, ZNF746) that plays an important role in...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716318125 |
| id |
doaj-123875aada7941409485885b4db0fc67 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Yunjong Lee Daniel A. Stevens Sung-Ung Kang Haisong Jiang Yun-Il Lee Han Seok Ko Leslie A. Scarffe George E. Umanah Hojin Kang Sangwoo Ham Tae-In Kam Kathleen Allen Saurav Brahmachari Jungwoo Wren Kim Stewart Neifert Seung Pil Yun Fabienne C. Fiesel Wolfdieter Springer Valina L. Dawson Joo-Ho Shin Ted M. Dawson |
| spellingShingle |
Yunjong Lee Daniel A. Stevens Sung-Ung Kang Haisong Jiang Yun-Il Lee Han Seok Ko Leslie A. Scarffe George E. Umanah Hojin Kang Sangwoo Ham Tae-In Kam Kathleen Allen Saurav Brahmachari Jungwoo Wren Kim Stewart Neifert Seung Pil Yun Fabienne C. Fiesel Wolfdieter Springer Valina L. Dawson Joo-Ho Shin Ted M. Dawson PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival Cell Reports parkin PINK1 PARIS ZNF746 ubiquitin PGC-1α Parkinson’s disease |
| author_facet |
Yunjong Lee Daniel A. Stevens Sung-Ung Kang Haisong Jiang Yun-Il Lee Han Seok Ko Leslie A. Scarffe George E. Umanah Hojin Kang Sangwoo Ham Tae-In Kam Kathleen Allen Saurav Brahmachari Jungwoo Wren Kim Stewart Neifert Seung Pil Yun Fabienne C. Fiesel Wolfdieter Springer Valina L. Dawson Joo-Ho Shin Ted M. Dawson |
| author_sort |
Yunjong Lee |
| title |
PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival |
| title_short |
PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival |
| title_full |
PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival |
| title_fullStr |
PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival |
| title_full_unstemmed |
PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival |
| title_sort |
pink1 primes parkin-mediated ubiquitination of paris in dopaminergic neuronal survival |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2017-01-01 |
| description |
Mutations in PTEN-induced putative kinase 1 (PINK1) and parkin cause autosomal-recessive Parkinson’s disease through a common pathway involving mitochondrial quality control. Parkin inactivation leads to accumulation of the parkin interacting substrate (PARIS, ZNF746) that plays an important role in dopamine cell loss through repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α) promoter activity. Here, we show that PARIS links PINK1 and parkin in a common pathway that regulates dopaminergic neuron survival. PINK1 interacts with and phosphorylates serines 322 and 613 of PARIS to control its ubiquitination and clearance by parkin. PINK1 phosphorylation of PARIS alleviates PARIS toxicity, as well as repression of PGC-1α promoter activity. Conditional knockdown of PINK1 in adult mouse brains leads to a progressive loss of dopaminergic neurons in the substantia nigra that is dependent on PARIS. Altogether, these results uncover a function of PINK1 to direct parkin-PARIS-regulated PGC-1α expression and dopaminergic neuronal survival. |
| topic |
parkin PINK1 PARIS ZNF746 ubiquitin PGC-1α Parkinson’s disease |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124716318125 |
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doaj-123875aada7941409485885b4db0fc672020-11-24T21:46:48ZengElsevierCell Reports2211-12472017-01-0118491893210.1016/j.celrep.2016.12.090PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal SurvivalYunjong Lee0Daniel A. Stevens1Sung-Ung Kang2Haisong Jiang3Yun-Il Lee4Han Seok Ko5Leslie A. Scarffe6George E. Umanah7Hojin Kang8Sangwoo Ham9Tae-In Kam10Kathleen Allen11Saurav Brahmachari12Jungwoo Wren Kim13Stewart Neifert14Seung Pil Yun15Fabienne C. Fiesel16Wolfdieter Springer17Valina L. Dawson18Joo-Ho Shin19Ted M. Dawson20Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADivision of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, South KoreaDivision of Pharmacology, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Suwon 440-746, South KoreaNeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USADepartment of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USANeuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAMutations in PTEN-induced putative kinase 1 (PINK1) and parkin cause autosomal-recessive Parkinson’s disease through a common pathway involving mitochondrial quality control. Parkin inactivation leads to accumulation of the parkin interacting substrate (PARIS, ZNF746) that plays an important role in dopamine cell loss through repression of proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α) promoter activity. Here, we show that PARIS links PINK1 and parkin in a common pathway that regulates dopaminergic neuron survival. PINK1 interacts with and phosphorylates serines 322 and 613 of PARIS to control its ubiquitination and clearance by parkin. PINK1 phosphorylation of PARIS alleviates PARIS toxicity, as well as repression of PGC-1α promoter activity. Conditional knockdown of PINK1 in adult mouse brains leads to a progressive loss of dopaminergic neurons in the substantia nigra that is dependent on PARIS. Altogether, these results uncover a function of PINK1 to direct parkin-PARIS-regulated PGC-1α expression and dopaminergic neuronal survival.http://www.sciencedirect.com/science/article/pii/S2211124716318125parkinPINK1PARISZNF746ubiquitinPGC-1αParkinson’s disease |