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Zc3h10 is a novel mitochondrial regulator
Author(s) -
Audano Matteo,
Pedretti Silvia,
Cermenati Gaia,
Brioschi Elisabetta,
Diaferia Giuseppe Riccardo,
Ghisletti Serena,
Cuomo Alessandro,
Bonaldi Tiziana,
Salerno Franco,
Mora Marina,
Grigore Liliana,
Garlaschelli Katia,
Baragetti Andrea,
Bonacina Fabrizia,
Catapano Alberico Luigi,
Norata Giuseppe Danilo,
Crestani Maurizio,
Caruso Donatella,
Saez Enrique,
De Fabiani Emma,
Mitro Nico
Publication year - 2018
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.201745531
Subject(s) - regulator , microbiology and biotechnology , biology , computational biology , genetics , gene
Mitochondria are the energy‐generating hubs of the cell. In spite of considerable advances, our understanding of the factors that regulate the molecular circuits that govern mitochondrial function remains incomplete. Using a genome‐wide functional screen, we identify the poorly characterized protein Zinc finger CCCH ‐type containing 10 (Zc3h10) as regulator of mitochondrial physiology. We show that Zc3h10 is upregulated during physiological mitochondriogenesis as it occurs during the differentiation of myoblasts into myotubes. Zc3h10 overexpression boosts mitochondrial function and promotes myoblast differentiation, while the depletion of Zc3h10 results in impaired myoblast differentiation, mitochondrial dysfunction, reduced expression of electron transport chain ( ETC ) subunits, and blunted TCA cycle flux. Notably, we have identified a loss‐of‐function mutation of Zc3h10 in humans (Tyr105 to Cys105) that is associated with increased body mass index, fat mass, fasting glucose, and triglycerides. Isolated peripheral blood mononuclear cells from individuals homozygotic for Cys105 display reduced oxygen consumption rate, diminished expression of some ETC subunits, and decreased levels of some TCA cycle metabolites, which all together derive in mitochondrial dysfunction. Taken together, our study identifies Zc3h10 as a novel mitochondrial regulator.