PINK1 controls mitochondrial localization of Parkin through direct phosphorylation

Kim, Yongsung; Park, Jeehye; Kim, Sunhong; Song, Saera; Kwon, Seok-Kyu; Lee, Sang‐Hee; Kitada, Tohru; Kim, Jin Man; Chung, Jongkyeong

doi:10.1016/j.bbrc.2008.10.104

Cited by 332 publications

(282 citation statements)

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“…Later studies have supported Narendra's findings showing that PINK1 acts upstream from Parkin, and that both proteins are recruited to depolarized mitochondria (Kim et al, 2008;Kawajiri et al, 2010;Matsuda et al, 2010;Vives-Bauza et al, 2010). The DJ-1 protein, already known by its antioxidant, chaperone-like and transcriptional modulator functions, has been recently proposed to act in parallel with PINK1 and…”

Section: Linking Oxidative Stress and Mitochondrial Dynamics In Pd Amentioning

confidence: 71%

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Morán

Moreno-Lastres

Marín-Buera

et al. 2012

Free Radical Biology and Medicine

140

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For decades mitochondria have been considered static round shaped organelles in charge of energy production. On the contrary, they are highly dynamic cellular components that undergo continuous cycles of fusion and fission influenced, for instance, by oxidative stress, cellular energy requirements, or the cell cycle state. New important functions beyond energy production have been attributed to mitochondria, such as the regulation of cell survival due to their role in the modulation of apoptosis, autophagy and aging. Primary mitochondrial diseases due to mutations in genes involved in these new mitochondrial functions, and the implication of mitochondrial dysfunction in multifactorial human pathologies like cancer, Alzheimer's and Parkinson's diseases, or diabetes has been demonstrated. Therefore, mitochondria are set at a central point of the equilibrium between health and disease, and a better understanding of mitochondrial functions will open new fields to explore the role of these mitochondrial pathways in human pathologies. The present review will dissect the relationships between the activity and assembly defects of the mitochondrial respiratory chain, oxidative damage, and alterations in mitochondrial dynamics, with special focus at their implications in neurodegeneration.

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Section: Linking Oxidative Stress and Mitochondrial Dynamics In Pd Amentioning

confidence: 71%

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Morán

Moreno-Lastres

Marín-Buera

et al. 2012

Free Radical Biology and Medicine

140

View full text Add to dashboard Cite

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Section: Parkin Protects Mitochondria Downstream Of Pink1mentioning

confidence: 99%

“…Using SH-SY5Y neuroblastoma cells and fly mutants, Kim et al (2008a) demonstrated that PINK1 translocates Parkin to mitochondria in a kinase activity-dependent manner. Additional biochemical analyses show that PINK1 phosphorylates Parkin and promotes its mitochondrial translocalization (Kim et al, 2008a). Further studies using mitochondrial uncoupling agents such as carbonyl cyanide m-chlorophenylhydrazone (CCCP) suggest that PINK1 selectively translocates Parkin to mitochondria with low membrane potential, confirming the exis- tence of PINK1-dependent Parkin translocation (Matsuda et al, 2010;Narendra et al, 2010a;Vives-Bauza et al, 2010).…”

Section: Parkin Protects Mitochondria Downstream Of Pink1mentioning

confidence: 99%

“…However, cell biological studies using human cells give opposite results. The co-expression of PINK1 and Parkin or expression of mitochondria-targeting Parkin causes mitochondria in human DA neuroblastoma cells to aggregate (Kim et al, 2008a). Moreover, PINK1 deficiency or point mutations induce mitochondrial fragmentation in immortal or primary human neuronal cells, indicating that PINK1 and Parkin inhibit mitochondrial fission in human neuronal cells (Exner et al, 2007;Kim et al, 2008a).…”

Section: Parkin Remodels Mitochondria By Ubquitinating Its Mitochondrmentioning

confidence: 99%

“…The co-expression of PINK1 and Parkin or expression of mitochondria-targeting Parkin causes mitochondria in human DA neuroblastoma cells to aggregate (Kim et al, 2008a). Moreover, PINK1 deficiency or point mutations induce mitochondrial fragmentation in immortal or primary human neuronal cells, indicating that PINK1 and Parkin inhibit mitochondrial fission in human neuronal cells (Exner et al, 2007;Kim et al, 2008a). Recently, several groups reported that the pro-mitochondrial fusion protein Marf and its human homolog, mitofusin (Mfn), are specifically ubiquitinated and degraded by Parkin in both human and Drosophila systems (Gegg et al, 2010;Tanaka et al, 2010;Ziviani et al, 2010).…”

Section: Parkin Remodels Mitochondria By Ubquitinating Its Mitochondrmentioning

confidence: 99%

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

Koh

Chung

2012

Molecules and Cells

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Parkinson's disease (PD), the most prevalent neurodegenerative movement disorder, is characterized by an agedependent 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 mitochondrial 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.

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