Syntaxin 17 regulates the localization and function of PGAM5 in mitochondrial division and mitophagy
| Autor: | Hana Kimura, Hiroki Inoue, Nobutaka Hattori, Tsuyoshi Inoshita, Jinglei Cheng, Mitsuo Tagaya, Naoshi Dohmae, Yuzuru Imai, Kohei Arasaki, Toshiki Amemiya, Yuichi Wakana, Toyoshi Fujimoto, Kahori Shiba-Fukushima, Masashi Sugo, Naohiko Hirota |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Dynamins Mitochondrial fission factor Ubiquitin-Protein Ligases PINK1 Mitochondrion Biology Syntaxin 17 Mitochondrial Dynamics General Biochemistry Genetics and Molecular Biology GTP Phosphohydrolases Mitochondrial Proteins 03 medical and health sciences 0302 clinical medicine Mitophagy Phosphoprotein Phosphatases Humans Molecular Biology General Immunology and Microbiology Qa-SNARE Proteins General Neuroscience Rhomboid protease PARL Autophagy Autophagosomes Membrane Proteins Articles Cell biology 030104 developmental biology Proteolysis Metalloproteases Microtubule-Associated Proteins Protein Kinases 030217 neurology & neurosurgery HeLa Cells Signal Transduction |
| Zdroj: | The EMBO journal. 37(21) |
| ISSN: | 1460-2075 |
| Popis: | PGAM5, a mitochondrial protein phosphatase that is genetically and biochemically linked to PINK1, facilitates mitochondrial division by dephosphorylating the mitochondrial fission factor Drp1. At the onset of mitophagy, PGAM5 is cleaved by PARL, a rhomboid protease that degrades PINK1 in healthy cells, and the cleaved form facilitates the engulfment of damaged mitochondria by autophagosomes by dephosphorylating the mitophagy receptor FUNDC1. Here, we show that the function and localization of PGAM5 are regulated by syntaxin 17 (Stx17), a mitochondria-associated membrane/mitochondria protein implicated in mitochondrial dynamics in fed cells and autophagy in starved cells. In healthy cells, loss of Stx17 causes PGAM5 aggregation within mitochondria and thereby failure of the dephosphorylation of Drp1, leading to mitochondrial elongation. In Parkin-mediated mitophagy, Stx17 is prerequisite for PGAM5 to interact with FUNDC1. Our results reveal that the Stx17-PGAM5 axis plays pivotal roles in mitochondrial division and PINK1/Parkin-mediated mitophagy. |
| Databáze: | OpenAIRE |
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