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024 7 _ |a 10.1016/j.mcpro.2021.100191
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037 _ _ |a DZNE-2022-00044
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Zittlau, Katharina I
|b 0
245 _ _ |a Temporal Analysis of Protein Ubiquitylation and Phosphorylation During Parkin-Dependent Mitophagy.
260 _ _ |a Bethesda, Md.
|c 2022
|b The American Society for Biochemistry and Molecular Biology
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500 _ _ |a (CC BY)
520 _ _ |a Mitophagy, the selective degradation of mitochondria by autophagy, affects defective mitochondria following damage or stress. At the onset of mitophagy, parkin ubiquitylates proteins on the mitochondrial outer membrane. While the role of parkin at the onset of mitophagy is well understood, less is known about its activity during later stages in the process. Here, we used HeLa cells expressing catalytically active or inactive parkin to perform temporal analysis of the proteome, ubiquitylome, and phosphoproteome during 18 h after induction of mitophagy by mitochondrial uncoupler carbonyl cyanide m-chlorophenyl hydrazine. Abundance profiles of proteins downregulated in parkin-dependent manner revealed a stepwise and 'outside-in' directed degradation of mitochondrial subcompartments. While ubiquitylation of mitochondrial outer membrane proteins was enriched among early parkin-dependent targets, numerous mitochondrial inner membrane, matrix, and cytosolic proteins were also found ubiquitylated at later stages of mitophagy. Phosphoproteome analysis revealed a possible crosstalk between phosphorylation and ubiquitylation during mitophagy on key parkin targets, such as voltage-dependent anion channel 2.
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650 _ 7 |a mitochondria
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650 _ 7 |a mitophagy
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650 _ 7 |a parkin
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650 _ 7 |a quantitative proteomics
|2 Other
650 _ 7 |a ubiquitin
|2 Other
650 _ 2 |a HeLa Cells
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mitophagy
|2 MeSH
650 _ 2 |a Phosphorylation
|2 MeSH
650 _ 2 |a Ubiquitin-Protein Ligases: metabolism
|2 MeSH
650 _ 2 |a Ubiquitination
|2 MeSH
700 1 _ |a Lechado-Terradas, Anna
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700 1 _ |a Nalpas, Nicolas
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700 1 _ |a Geisler, Sven
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700 1 _ |a Kahle, Philipp J
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700 1 _ |a Macek, Boris
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773 _ _ |a 10.1016/j.mcpro.2021.100191
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|t Molecular & cellular proteomics
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