Suppressor of cytokine signaling 6 (SOCS6) promotes mitochondrial fission via regulating DRP1 translocation
| Autor: | Huan-Yu Lin, R. C. Lin, S. T. Lin, Hsin Chen Lee, R. H. Lai, Fung-Fang Wang, Chih Ching Lin, Mei Jung Wang, Jeou-Yuan Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Dynamins
Suppressor of Cytokine Signaling Proteins DRP1 Mitochondrion Biology Mitochondrial apoptosis-induced channel Mitochondrial Dynamics GTP Phosphohydrolases Mitochondrial Proteins mitochondrial dynamic Phosphoprotein Phosphatases Humans Gene Silencing Phosphorylation Molecular Biology HSPA9 Original Paper SOCS6 apoptosis Cell Biology Cell biology Mitochondria Protein Transport HEK293 Cells mitochondrial fusion Gene Knockdown Techniques DNAJA3 Apoptosis-inducing factor Mitochondrial fission ATP–ADP translocase Carrier Proteins Microtubule-Associated Proteins PGAM5 Signal Transduction |
| Zdroj: | Cell Death and Differentiation |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | Mitochondria are highly motile organelles that constantly undergo fission and fusion. Impairment of mitochondrial dynamics is associated with mitochondrial dysfunction and is frequently linked to the pathogenesis of neurodegenerative diseases and cancer. We have previously shown that biallelic inactivation of the suppressor of cytokine signaling 6 (SOCS6) gene is a frequent event in human gastric cancer. In this study, we recapitulated the event of SOCS6 loss using a Lentivirus-based knockdown approach, and demonstrated the linkage between SOCS6 depletion and the suppression of programmed cell death. SOCS6 promotes intrinsic apoptosis, with increased Bax conformational change, mitochondrial targeting, and oligomerization. Most importantly, SOCS6 is targeted to mitochondria and induces mitochondrial fragmentation mediated through an increase in DRP1 fission activity. Here, we show that SOCS6 forms complex with DRP1 and the mitochondrial phosphatase PGAM5, attenuates DRP1 phosphorylation, and promotes DRP1 mitochondrial translocation. Based on mutation analyses, SOCS6-mediated apoptosis is tightly coupled to its ability to induce mitochondrial fission. This study demonstrates an important role for SOCS6 in modulating mitochondrial dynamics and apoptosis. |
| Databáze: | OpenAIRE |
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