Tollip coordinates Parkin‐dependent trafficking of mitochondrial‐derived vesicles
| Autor: | David A. Tumbarello, Thomas A. Ryan, Charlotte L Collier, Rebecca E Wood, Emelia A Assar, Daniel Routledge, Elliott O Phillips, Alice J B Robinson |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Retromer
Endosome Parkinson's disease Ubiquitin-Protein Ligases Receptors Cell Surface Endosomes Article vesicle transport General Biochemistry Genetics and Molecular Biology Parkin 03 medical and health sciences 0302 clinical medicine Mitochondrial Precursor Protein Import Complex Proteins Mitophagy Humans Ligase activity Membrane & Intracellular Transport Molecular Biology Late endosome 030304 developmental biology 0303 health sciences General Immunology and Microbiology biology membrane trafficking General Neuroscience TOLLIP Intracellular Signaling Peptides and Proteins Membrane Transport Proteins Articles Mitochondria nervous system diseases Ubiquitin ligase Cell biology Protein Transport HEK293 Cells lysosome biology.protein Lysosomes 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | The EMBO Journal |
| ISSN: | 1460-2075 0261-4189 |
| Popis: | Multiple mitochondrial quality control pathways exist to maintain the health of mitochondria and ensure cell homeostasis. Here, we investigate the role of the endosomal adaptor Tollip during the mitochondrial stress response and identify its interaction and colocalisation with the Parkinson's disease‐associated E3 ubiquitin ligase Parkin. The interaction between Tollip and Parkin is dependent on the ubiquitin‐binding CUE domain of Tollip, but independent of Tom1 and mitophagy. Interestingly, this interaction is independent of Parkin mitochondrial recruitment and ligase activity but requires an intact ubiquitin‐like (UBL) domain. Importantly, Tollip regulates Parkin‐dependent endosomal trafficking of a discrete subset of mitochondrial‐derived vesicles (MDVs) to facilitate delivery to lysosomes. Retromer function and an interaction with Tom1 allow Tollip to facilitate late endosome/lysosome trafficking in response to mitochondrial stress. We find that upregulation of TOM20‐positive MDVs upon mitochondrial stress requires Tollip interaction with ubiquitin, endosomal membranes and Tom1 to ensure their trafficking to the lysosomes. Thus, we conclude that Tollip, via an association with Parkin, is an essential coordinator to sort damaged mitochondrial‐derived cargo to the lysosomes. Vesicles induced by mitochondrial stress are routed towards lysosomes and degradation by the endosomal adaptor Tollip and the ubiquitin E3 ligase Parkin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text