Back to Search
Start Over
Drp1 overexpression induces desmin disassembling and drives kinesin-1 activation promoting mitochondrial trafficking in skeletal muscle
- Source :
- Cell Death and Differentiation
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group UK, 2020.
-
Abstract
- Mitochondria change distribution across cells following a variety of pathophysiological stimuli. The mechanisms presiding over this redistribution are yet undefined. In a murine model overexpressing Drp1 specifically in skeletal muscle, we find marked mitochondria repositioning in muscle fibres and we demonstrate that Drp1 is involved in this process. Drp1 binds KLC1 and enhances microtubule-dependent transport of mitochondria. Drp1-KLC1 coupling triggers the displacement of KIF5B from kinesin-1 complex increasing its binding to microtubule tracks and mitochondrial transport. High levels of Drp1 exacerbate this mechanism leading to the repositioning of mitochondria closer to nuclei. The reduction of Drp1 levels decreases kinesin-1 activation and induces the partial recovery of mitochondrial distribution. Drp1 overexpression is also associated with higher cyclin-dependent kinase-1 (Cdk-1) activation that promotes the persistent phosphorylation of desmin at Ser-31 and its disassembling. Fission inhibition has a positive effect on desmin Ser-31 phosphorylation, regardless of Cdk-1 activation, suggesting that induction of both fission and Cdk-1 are required for desmin collapse. This altered desmin architecture impairs mechanotransduction and compromises mitochondrial network stability priming mitochondria transport through microtubule-dependent trafficking with a mechanism that involves the Drp1-dependent regulation of kinesin-1 complex.
- Subjects :
- Dynamins
endocrine system
Cell biology
Kinesins
macromolecular substances
Mitochondrion
Biochemistry
Microtubules
Article
Desmin
DNM1L
Phosphoserine
CDC2 Protein Kinase
medicine
Myocyte
Animals
Humans
Phosphorylation
Muscle, Skeletal
Molecular Biology
Mitochondrial transport
Quinazolinones
Chemistry
Skeletal muscle
Transport protein
Mitochondria
Enzyme Activation
Mice, Inbred C57BL
Succinate Dehydrogenase
Protein Transport
medicine.anatomical_structure
Kinesin
Subjects
Details
- Language :
- English
- ISSN :
- 14765403 and 13509047
- Volume :
- 27
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cell Death and Differentiation
- Accession number :
- edsair.doi.dedup.....75c4ff3980b16391dfb985897a833466