ArticleScientific reports2019
The PINK1 kinase-driven ubiquitin ligase Parkin promotes mitochondrial protein import through the presequence pathway in living cells.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 55 citations in OpenAlex.
- Review
- Autophagy and mitophagy at the synapse and beyond: implications for learning, memory and neurological disorders.Autophagy · 2026Review
- The role of SIRT3 in homeostasis and cellular health.Frontiers in cellular neuroscience · 2024Review
- Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy.Experimental & molecular medicine · 2023Article
- Parkin drives pS65-Ub turnover independently of canonical autophagy in Drosophila.EMBO reports · 2022Article
- Mitochondria in neurodegeneration.Current opinion in physiology · 2022Article
- Role of the mtDNA Mutations and Mitophagy in Inflammaging.International journal of molecular sciences · 2022Review
- PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis.Stem cell research & therapy · 2021Article
- Nanomedicine for Neurodegenerative Disorders: Focus on Alzheimer's and Parkinson's Diseases.International journal of molecular sciences · 2021Review
- Interplay between Mitochondrial Protein Import and Respiratory Complexes Assembly in Neuronal Health and Degeneration.Life (Basel, Switzerland) · 2021Review
- Review
- The cell biology of Parkinson's disease.The Journal of cell biology · 2021Review
- Mitochondrial Protein Import Dysfunction in Pathogenesis of Neurodegenerative Diseases.Molecular neurobiology · 2021Review
- The Mitochondrial Kinase PINK1 in Diabetic Kidney Disease.International journal of molecular sciences · 2021Review
- The Mitochondrial Outer Membrane Protein Tom70-Mediator in Protein Traffic, Membrane Contact Sites and Innate Immunity.International journal of molecular sciences · 2020Review
- PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson's disease.Molecular neurodegeneration · 2020Review
- PINK1/Parkin Mediated Mitophagy, CaInternational journal of molecular sciences · 2020Review
- Global Landscape and Dynamics of Parkin and USP30-Dependent Ubiquitylomes in iNeurons during Mitophagic Signaling.Molecular cell · 2020Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Most of over a thousand mitochondrial proteins are encoded by nuclear genes and must be imported from the cytosol. Little is known about the cytosolic events regulating mitochondrial protein import, partly due to the lack of appropriate tools for its assessment in living cells. We engineered an inducible biosensor for monitoring the main presequence-mediated import pathway with a quantitative, luminescence-based readout. This tool was used to explore the regulation of mitochondrial import by the PINK1 kinase-driven Parkin ubiquitin ligase, which is dysfunctional in autosomal recessive Parkinson's disease. We show that mitochondrial import was stimulated by Parkin, but not by disease-causing Parkin variants. This effect was dependent on Parkin activation by PINK1 and accompanied by an increase in the abundance of K11 ubiquitin chains on mitochondria and by ubiquitylation of subunits of the translocase of outer mitochondrial membrane. Mitochondrial import efficiency was abnormally low in cells from patients with PINK1- and PARK2-linked Parkinson's disease and was restored by phosphomimetic ubiquitin in cells with residual Parkin activity. Altogether, these findings uncover a role of ubiquitylation in mitochondrial import regulation and suggest that loss of this regulatory loop may underlie the pathophysiology of Parkinson's disease, providing novel opportunities for therapeutic intervention.
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