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Chemical targeting of NEET proteins reveals their function in mitochondrial morphodynamics
- Source :
- EMBO Rep, EMBO Reports, EMBO Reports, EMBO Press, 2020, 21 (12), ⟨10.15252/embr.201949019⟩, EMBO Reports, EMBO Press, 2020, ⟨10.15252/embr.201949019⟩
- Publication Year :
- 2019
-
Abstract
- International audience; Several human pathologies including neurological, cardiac, infectious , cancerous, and metabolic diseases have been associated with altered mitochondria morphodynamics. Here, we identify a small organic molecule, which we named Mito-C. Mito-C is targeted to mitochondria and rapidly provokes mitochondrial network fragmentation. Biochemical analyses reveal that Mito-C is a member of a new class of heterocyclic compounds that target the NEET protein family, previously reported to regulate mito-chondrial iron and ROS homeostasis. One of the NEET proteins, NAF-1, is identified as an important regulator of mitochondria morphodynamics that facilitates recruitment of DRP1 to the ER-mitochondria interface. Consistent with the observation that certain viruses modulate mitochondrial morphogenesis as a necessary part of their replication cycle, Mito-C counteracts dengue virus-induced mitochondrial network hyperfusion and represses viral replication. The newly identified chemical class including Mito-C is of therapeutic relevance for pathologies where altered mitochondria dynamics is part of disease etiology and NEET proteins are highlighted as important therapeutic targets in anti-viral research.
- Subjects :
- Protein family
Iron
morphodynamics
Regulator
Morphogenesis
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Mitochondrion
Biology
Microbiology
Biochemistry
contact sites
virus Subject Categories Membranes & Trafficking
Mitochondrial Proteins
03 medical and health sciences
0302 clinical medicine
Genetics
Homeostasis
Humans
Fragmentation (cell biology)
Molecular Biology
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
0303 health sciences
Disease etiology
3. Good health
Cell biology
Mitochondria
Virology & Host Pathogen Interaction
Viral replication
NEET proteins
030217 neurology & neurosurgery
Function (biology)
Reports
Subjects
Details
- ISSN :
- 14693178 and 1469221X
- Volume :
- 21
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- EMBO reports
- Accession number :
- edsair.doi.dedup.....d05b0954eedbb6d731ad6194e35c1b2c