Abstract
| Original language | English |
|---|---|
| Journal | EMBO Reports |
| Volume | 19 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2018 |
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Keywords
- functional screens
- metabolism
- mitochondria
- Zc3h10
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Zc3h10 is a novel mitochondrial regulator. / 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.
In: EMBO Reports, Vol. 19, No. 4, 01.04.2018.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Zc3h10 is a novel mitochondrial regulator
AU - Audano, Matteo
AU - Pedretti, Silvia
AU - Cermenati, Gaia
AU - Brioschi, Elisabetta
AU - Diaferia, Giuseppe Riccardo
AU - Ghisletti, Serena
AU - Cuomo, Alessandro
AU - Bonaldi, Tiziana
AU - Salerno, Franco
AU - Mora, Marina
AU - Grigore, Liliana
AU - Garlaschelli, Katia
AU - Baragetti, Andrea
AU - Bonacina, Fabrizia
AU - Catapano, Alberico Luigi
AU - Norata, Giuseppe Danilo
AU - Crestani, Maurizio
AU - Caruso, Donatella
AU - Saez, Enrique
AU - De Fabiani, Emma
AU - Mitro, Nico
N1 - M1 - e45531
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
KW - functional screens
KW - metabolism
KW - mitochondria
KW - Zc3h10
U2 - 10.15252/embr.201745531
DO - 10.15252/embr.201745531
M3 - Article
VL - 19
JO - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
IS - 4
ER -