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A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30
- Source :
- Cell research. 24(4)
- Publication Year :
- 2013
-
Abstract
- Mitochondrial 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 (S3) that potently induced mitochondrial fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in either Mfn1 or Mfn2. A mitochondria-localized deubiquitinase USP30 is a target of S3. The inhibition of USP30 by S3 leads to an increase of non-degradative ubiquitination of Mfn1/2, which enhances Mfn1 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.
- Subjects :
- MFN2
Mitochondrial Dynamics
Mitochondrial Membrane Transport Proteins
Oxidative Phosphorylation
GTP Phosphohydrolases
Mitochondrial Proteins
Mitochondrial membrane transport protein
Gene Knockout Techniques
Mice
MFN1
Animals
Humans
Enzyme Inhibitors
Molecular Biology
Cells, Cultured
Mitochondrial DNA inheritance
biology
Cell Biology
Research Highlight
Cell biology
Mitochondria
mitochondrial fusion
DNAJA3
biology.protein
Original Article
Mitochondrial fission
ATP–ADP translocase
Thiolester Hydrolases
Ubiquitin-Specific Proteases
Diterpenes
HeLa Cells
Subjects
Details
- ISSN :
- 17487838
- Volume :
- 24
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cell research
- Accession number :
- edsair.doi.dedup.....192873ace1fb5b0ce76c2e51b1a20877