Cell research, 2014-04, Vol.24 (4), p.482-496
2014
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Details
- Autor(en) / Beteiligte
- Titel
- A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30
- Ist Teil von
- Cell research, 2014-04, Vol.24 (4), p.482-496
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Mitocbondrial fusion is a highly coordinated process that mixes and unifies the mitochondrial compartment for normal mitochondrial functions and mitochondrial DNA inheritance. Dysregulated mitochondrial fusion causes mitochondrial fragmentation, abnormal mitochondrial physiology and inheritance, and has been causally linked with a number of neuronal diseases. Here, we identified a diterpenoid derivative 15-oxospiramilactone （$3） that potently induced mitochondrial fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in either Mfnl or Mfn2. A mitochondria-localized deubiquitinase USP30 is a target of $3. The inhibition of USP30 by $3 leads to an increase of non-degradative ubiquitination of Mfnl/2, which enhances Mfnl and Mfn2 activity and promotes mitochondrial fusion. Thus, through the use of an inhibitor of USP30, our study uncovers an unconventional function of non-degradative ubiquitination of Mfns in promoting mitochondrial fusion.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1001-0602eISSN: 1748-7838DOI: 10.1038/cr.2014.20Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3975501
- Format
- –
- Schlagworte
- 631/80/313/2378, 631/80/458/582, 631/80/642/333, Animals, Cell Biology, Cells, Cultured, Diterpenes - pharmacology, DNA遗传, Enzyme Inhibitors - pharmacology, Gene Knockout Techniques, GTP Phosphohydrolases - genetics, HeLa Cells, Humans, Life Sciences, Mice, Mitochondria - drug effects, Mitochondria - metabolism, Mitochondrial DNA, Mitochondrial Dynamics - drug effects, Mitochondrial Membrane Transport Proteins - genetics, Mitochondrial Proteins - antagonists & inhibitors, Mitochondrial Proteins - genetics, Original, original-article, Oxidative Phosphorylation - drug effects, Physiology, Respiration, Thiolester Hydrolases - antagonists & inhibitors, Ubiquitin-Specific Proteases - antagonists & inhibitors, 体功能, 分子, 天然, 泛素化, 神经元, 线粒体, 衍生物