Premium
Chemical targeting of NEET proteins reveals their function in mitochondrial morphodynamics
Author(s) -
Molino Diana,
PilaCastellanos Irene,
Marjault HenriBaptiste,
Dias Amoedo Nivea,
Kopp Katja,
Rochin Leila,
Karmi Ola,
Sohn YangSung,
Lines Laetitia,
Hamaï Ahmed,
Joly Stéphane,
Radreau Pauline,
Vonderscher Jacky,
Codogno Patrice,
Giordano Francesca,
Machin Peter,
Rossignol Rodrigue,
Meldrum Eric,
Arnoult Damien,
Ruggieri Alessia,
Nechushtai Rachel,
de Chassey Benoit,
Morel Etienne
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201949019
Subject(s) - mitochondrion , biology , microbiology and biotechnology
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.