Zc3h10 is a novel mitochondrial regulator
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal Article |
| Published: |
Wiley-Blackwell Publishing Ltd.
2018
|
| Online Access: | http://hdl.handle.net/20.500.11937/66790 |
| _version_ | 1848761393364336640 |
|---|---|
| author | Audano, M. Pedretti, S. Cermenati, G. Brioschi, E. Diaferia, G. Ghisletti, S. Cuomo, A. Bonaldi, T. Salerno, F. Mora, M. Grigore, L. Garlaschelli, K. Baragetti, A. Bonacina, F. Catapano, A. Norata, Giuseppe Crestani, M. Caruso, D. Saez, E. De Fabiani, E. Mitro, N. |
| author_facet | Audano, M. Pedretti, S. Cermenati, G. Brioschi, E. Diaferia, G. Ghisletti, S. Cuomo, A. Bonaldi, T. Salerno, F. Mora, M. Grigore, L. Garlaschelli, K. Baragetti, A. Bonacina, F. Catapano, A. Norata, Giuseppe Crestani, M. Caruso, D. Saez, E. De Fabiani, E. Mitro, N. |
| author_sort | Audano, M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T10:30:57Z |
| format | Journal Article |
| id | curtin-20.500.11937-66790 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:30:57Z |
| publishDate | 2018 |
| publisher | Wiley-Blackwell Publishing Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-667902018-10-12T01:28:13Z Zc3h10 is a novel mitochondrial regulator Audano, M. Pedretti, S. Cermenati, G. Brioschi, E. Diaferia, G. Ghisletti, S. Cuomo, A. Bonaldi, T. Salerno, F. Mora, M. Grigore, L. Garlaschelli, K. Baragetti, A. Bonacina, F. Catapano, A. Norata, Giuseppe Crestani, M. Caruso, D. Saez, E. De Fabiani, E. Mitro, N. 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/66790 10.15252/embr.201745531 Wiley-Blackwell Publishing Ltd. fulltext |
| spellingShingle | Audano, M. Pedretti, S. Cermenati, G. Brioschi, E. Diaferia, G. Ghisletti, S. Cuomo, A. Bonaldi, T. Salerno, F. Mora, M. Grigore, L. Garlaschelli, K. Baragetti, A. Bonacina, F. Catapano, A. Norata, Giuseppe Crestani, M. Caruso, D. Saez, E. De Fabiani, E. Mitro, N. Zc3h10 is a novel mitochondrial regulator |
| title | Zc3h10 is a novel mitochondrial regulator |
| title_full | Zc3h10 is a novel mitochondrial regulator |
| title_fullStr | Zc3h10 is a novel mitochondrial regulator |
| title_full_unstemmed | Zc3h10 is a novel mitochondrial regulator |
| title_short | Zc3h10 is a novel mitochondrial regulator |
| title_sort | zc3h10 is a novel mitochondrial regulator |
| url | http://hdl.handle.net/20.500.11937/66790 |