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Chemical targeting of NEET proteins reveals their function in mitochondrial morphodynamics

Abstract 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...

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Main Authors: Molino, Diana (Author) , Pila-Castellanos, Irene (Author) , Marjault, Henri-Baptiste (Author) , Dias Amoedo, Nivea (Author) , Kopp, Katja (Author) , Rochin, Leila (Author) , Karmi, Ola (Author) , Sohn, Yang-Sung (Author) , Lines, Laetitia (Author) , Hamaï, Ahmed (Author) , Joly, Stéphane (Author) , Radreau, Pauline (Author) , Vonderscher, Jacky (Author) , Codogno, Patrice (Author) , Giordano, Francesca (Author) , Machin, Peter (Author) , Rossignol, Rodrigue (Author) , Meldrum, Eric (Author) , Arnoult, Damien (Author) , Ruggieri, Alessia (Author) , Nechushtai, Rachel (Author) , de Chassey, Benoit (Author) , Morel, Etienne (Author)
Format: Article (Journal)
Language:English
Published: 12 November 2020
In: EMBO reports
Year: 2020, Volume: 21, Issue: 12, Pages: 1-12
ISSN:1469-3178
DOI:10.15252/embr.201949019
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/embr.201949019
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/embr.201949019
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Author Notes:Diana Molino, Irene Pila-Castellanos, Henri-Baptiste Marjault, Nivea Dias Amoedo, Katja Kopp, Leila Rochin, Ola Karmi, Yang-Sung Sohn, Laetitia Lines, Ahmed Hamaï, Stéphane Joly, Pauline Radreau, Jacky Vonderscher, Patrice Codogno, Francesca Giordano, Peter Machin, Rodrigue Rossignol, Eric Meldrum, Damien Arnoult, Alessia Ruggieri, Rachel Nechushtai, Benoit de Chassey & Etienne Morel
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Summary:Abstract 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 mitochondrial 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.
Item Description:Gesehen am 20.01.2021
Physical Description:Online Resource
ISSN:1469-3178
DOI:10.15252/embr.201949019

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