Zc3h10 is a novel mitochondrial regulator

被引：26

作者：

Audano, Matteo ^{[1
]}

Pedretti, Silvia ^{[1
]}

Cermenati, Gaia ^{[1
]}

Brioschi, Elisabetta ^{[1
]}

Diaferia, Giuseppe Riccardo ^{[2
]}

Ghisletti, Serena ^{[3
]}

Cuomo, Alessandro ^{[2
]}

Bonaldi, Tiziana ^{[2
]}

Salerno, Franco ^{[4
]}

Mora, Marina ^{[4
]}

Grigore, Liliana ^{[5
,6
]}

Garlaschelli, Katia ^{[6
]}

Baragetti, Andrea ^{[1
,6
]}

Bonacina, Fabrizia ^{[1
]}

Catapano, Alberico Luigi ^{[1
,5
]}

Norata, Giuseppe Danilo ^{[1
,6
,7
]}

Crestani, Maurizio ^{[1
]}

Caruso, Donatella ^{[1
]}

Saez, Enrique ^{[8
]}

De Fabiani, Emma ^{[1
]}

Mitro, Nico ^{[1
]}

机构：

[1] Univ Milan, Dipartimento Sci Farmacol & Biomol, DiSFeB, Milan, Italy

[2] European Inst Oncol IEO, Dept Expt Oncol, Milan, Italy

[3] Humanitas Clin & Res Ctr, Rozzano Milan, Italy

[4] Fdn IRCCS C Besta, Neurol Inst, Neuromuscular Dis & Neuroimmunol Unit, Milan, Italy

[5] IRCSS Multimed, Milan, Italy

[6] Bassini Hosp, SISA Ctr, Cinisello Balsamo, Italy

[7] Curtin Univ, Fac Hlth Sci, Curtin Hlth Innovat Res Inst, Sch Biomed Sci, Perth, WA, Australia

[8] Scripps Res Inst, Dept Mol Med, La Jolla, CA 92037 USA

来源：

EMBO REPORTS | 2018年 / 19卷 / 04期

关键词：

functional screens; metabolism; mitochondria; Zc3h10; BINDING-PROTEIN; GENE-EXPRESSION; RNA GRANULES; COMPUTATIONAL PLATFORM; TRANSCRIPTION FACTOR; SKELETAL-MUSCLE; MESSENGER-RNAS; BIOGENESIS; MASS; NUCLEAR;

D O I：

10.15252/embr.201745531

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：16

共 55 条

[1] A method and server for predicting damaging missense mutations [J].