Abstract
Original language | English |
---|---|
Journal | EMBO Reports |
Volume | 19 |
Issue number | 4 |
Publication status | Published - 2018 |
Keywords
- functional screens
- metabolism
- mitochondria
- Zc3h10
- genomic DNA
- glucose
- regulator protein
- triacylglycerol
- unclassified drug
- Zinc finger CCCH type containing 10
- aged
- animal experiment
- animal tissue
- Article
- body mass
- cell differentiation
- cell isolation
- citric acid cycle
- controlled study
- embryo
- fat mass
- female
- gene overexpression
- glucose blood level
- homozygote
- human
- human cell
- human tissue
- loss of function mutation
- male
- mitochondrial biogenesis
- mitochondrion
- mouse
- myoblast
- myotube
- nonhuman
- oxygen consumption
- peripheral blood mononuclear cell
- priority journal
- protein depletion
- protein expression
- protein function
- protein subunit
- respiratory chain
- triacylglycerol blood level
- upregulation
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Zc3h10 is a novel mitochondrial regulator. / Audano, M.; Pedretti, S.; Cermenati, G. et al.
In: EMBO Reports, Vol. 19, No. 4, 2018.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Zc3h10 is a novel mitochondrial regulator
AU - Audano, M.
AU - Pedretti, S.
AU - Cermenati, G.
AU - Brioschi, E.
AU - Diaferia, G.R.
AU - Ghisletti, S.
AU - Cuomo, A.
AU - Bonaldi, T.
AU - Salerno, F.
AU - Mora, M.
AU - Grigore, L.
AU - Garlaschelli, K.
AU - Baragetti, A.
AU - Bonacina, F.
AU - Catapano, A.L.
AU - Norata, G.D.
AU - Crestani, M.
AU - Caruso, D.
AU - Saez, E.
AU - De Fabiani, E.
AU - Mitro, N.
N1 - Export Date: 5 February 2019 CODEN: ERMEA Correspondence Address: De Fabiani, E.; DiSFeB, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di MilanoItaly; email: emma.defabiani@unimi.it Chemicals/CAS: glucose, 50-99-7, 84778-64-3 Funding details: Ministero della Salute, GR-2011-02346974, 2016-WI218287, GR-2013-02355011 Funding details: Associazione Italiana per la Ricerca sul Cancro, AIRC Funding details: Eli Lilly and Company Funding details: College of Natural Resources, University of California Berkeley, CNR Funding details: European Foundation for the Study of Diabetes, EFSD Funding details: Fondazione Cariplo, 2015-0524, 2016-0852, 2014-0991, 2015-0564 Funding details: RF-GR2011 Funding text 1: We thank F. Giavarini for his valuable help with HPLC and mass spectrometry. We also thank A. Maggi for critically reading the manuscript and for her helpful comments and all the members of the laboratory for valuable discussion. We are in debt with Ms. E. Desiderio Pinto for administrative assistance. T. Bonaldi is supported by grants from the Italian Association for Cancer Research (AIRC), the Italian Ministry of Health (RF-GR2011), and the Epigen Flagship project grant (CNR). This work is supported by Ministero della Salute GR-2011-02346974 to GDN and GR-2013-02355011 to FB; Aspire Cardiovascular Grant 2016-WI218287 to GDN, The Giovanni Armenise Harvard-Foundation Career Development Grant, Cariplo Foundation (grant number 2014-0991 to NM, 2015-0524 and 2015-0564 to ALC, 2016-0852 to GDN), European Foundation for the Study of Diabetes (EFSD)/Lilly European Diabetes Research Programme 2015 to N.M. This research was supported by grants from MIUR Progetto Eccellenza. References: Evans, A., Neuman, N., The mighty mitochondria (2016) Mol Cell, 61, p. 641; Nunnari, J., Suomalainen, A., Mitochondria: in sickness and in health (2012) Cell, 148, pp. 1145-1159; Suomalainen, A., Isohanni, P., Mitochondrial DNA depletion syndromes–many genes, common mechanisms (2010) Neuromuscul Disord, 20, pp. 429-437; Schon, E.A., DiMauro, S., Hirano, M., Human mitochondrial DNA: roles of inherited and somatic mutations (2012) Nat Rev Genet, 13, pp. 878-890; Lowell, B.B., Shulman, G.I., Mitochondrial dysfunction and type 2 diabetes (2005) Science, 307, pp. 384-387; Ramadasan-Nair, R., Gayathri, N., Mishra, S., Sunitha, B., Mythri, R.B., Nalini, A., Subbannayya, Y., Srinivas Bharath, M.M., Mitochondrial alterations and oxidative stress in an acute transient mouse model of muscle degeneration: implications for muscular dystrophy and related muscle pathologies (2013) J Biol Chem, 289, pp. 485-509; Andreux, P.A., Houtkooper, R.H., Auwerx, J., Pharmacological approaches to restore mitochondrial function (2013) Nat Rev Drug Discov, 12, pp. 465-483; Larsson, N.G., Wang, J., Wilhelmsson, H., Oldfors, A., Rustin, P., Lewandoski, M., Barsh, G.S., Clayton, D.A., Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice (1998) Nat Genet, 18, pp. 231-236; Calvo, S.E., Clauser, K.R., Mootha, V.K., MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins (2016) Nucleic Acids Res, 44, pp. D1251-D1257; Kohler, A., Hurt, E., Exporting RNA from the nucleus to the cytoplasm (2007) Nat Rev Mol Cell Biol, 8, pp. 761-773; Chandel, N.S., Evolution of mitochondria as signaling organelles (2015) Cell Metab, 22, pp. 204-206; van der Knaap, J.A., Verrijzer, C.P., Undercover: gene control by metabolites and metabolic enzymes (2016) Genes Dev, 30, pp. 2345-2369; Su, X., Wellen, K.E., Rabinowitz, J.D., Metabolic control of methylation and acetylation (2015) Curr Opin Chem Biol, 30, pp. 52-60; Scarpulla, R.C., Vega, R.B., Kelly, D.P., Transcriptional integration of mitochondrial biogenesis (2012) Trends Endocrinol Metab, 23, pp. 459-466; Hock, M.B., Kralli, A., Transcriptional control of mitochondrial biogenesis and function (2009) Annu Rev Physiol, 71, pp. 177-203; Wu, Z., Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1 (1999) Cell, 98, p. 115; Fan, M., Rhee, J., St-Pierre, J., Handschin, C., Puigserver, P., Lin, J., Jaeger, S., Spiegelman, B.M., Suppression of mitochondrial respiration through recruitment of p160 myb binding protein to PGC-1alpha: modulation by p38 MAPK (2004) Genes Dev, 18, pp. 278-289; Duguez, S., Feasson, L., Denis, C., Freyssenet, D., Mitochondrial biogenesis during skeletal muscle regeneration (2002) Am J Physiol Endocrinol Metab, 282, pp. E802-E809; Remels, A.H., Langen, R.C., Schrauwen, P., Schaart, G., Schols, A.M., Gosker, H.R., Regulation of mitochondrial biogenesis during myogenesis (2010) Mol Cell Endocrinol, 315, pp. 113-120; Moyes, C.D., Mathieu-Costello, O.A., Tsuchiya, N., Filburn, C., Hansford, R.G., Mitochondrial biogenesis during cellular differentiation (1997) Am J Physiol, 272, pp. C1345-C1351; Hu, C.J., Wang, L.Y., Chodosh, L.A., Keith, B., Simon, M.C., Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation (2003) Mol Cell Biol, 23, pp. 9361-9374; Adzhubei, I.A., Schmidt, S., Peshkin, L., Ramensky, V.E., Gerasimova, A., Bork, P., Kondrashov, A.S., Sunyaev, S.R., A method and server for predicting damaging missense mutations (2010) Nat Methods, 7, pp. 248-249; Norata, G.D., Garlaschelli, K., Ongari, M., Raselli, S., Grigore, L., Catapano, A.L., Effects of fractalkine receptor variants on common carotid artery intima-media thickness (2006) Stroke, 37, pp. 1558-1561; Norata, G.D., Garlaschelli, K., Grigore, L., Tibolla, G., Raselli, S., Redaelli, L., Buccianti, G., Catapano, A.L., Circulating soluble receptor for advanced glycation end products is inversely associated with body mass index and waist/hip ratio in the general population (2009) Nutrition Metab Cardiovasc Dis, 19, pp. 129-134; Lorenz, M.W., Polak, J.F., Kavousi, M., Mathiesen, E.B., Volzke, H., Tuomainen, T.P., Sander, D., Robertson, C.M., Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data (2012) Lancet, 379, pp. 2053-2062; Baragetti, A., Palmen, J., Garlaschelli, K., Grigore, L., Pellegatta, F., Tragni, E., Catapano, A.L., Talmud, P.J., Telomere shortening over 6 years is associated with increased subclinical carotid vascular damage and worse cardiovascular prognosis in the general population (2015) J Intern Med, 277, pp. 478-487; Su, A.I., Cooke, M.P., Ching, K.A., Hakak, Y., Walker, J.R., Wiltshire, T., Orth, A.P., Moqrich, A., Large-scale analysis of the human and mouse transcriptomes (2002) Proc Natl Acad Sci USA, 99, pp. 4465-4470; Patananan, A.N., Wu, T.H., Chiou, P.Y., Teitell, M.A., Modifying the mitochondrial genome (2016) Cell Metab, 23, pp. 785-796; Wolf, A.R., Mootha, V.K., Functional genomic analysis of human mitochondrial RNA processing (2014) Cell Rep, 7, pp. 918-931; Arroyo, J.D., Jourdain, A.A., Calvo, S.E., Ballarano, C.A., Doench, J.G., Root, D.E., Mootha, V.K., A genome-wide CRISPR death screen identifies genes essential for oxidative phosphorylation (2016) Cell Metab, 24, pp. 875-885; Hall, T.M., Multiple modes of RNA recognition by zinc finger proteins (2005) Curr Opin Struct Biol, 15, pp. 367-373; Liang, J., Song, W., Tromp, G., Kolattukudy, P.E., Fu, M., Genome-wide survey and expression profiling of CCCH-zinc finger family reveals a functional module in macrophage activation (2008) PLoS One, 3; Castello, A., Fischer, B., Eichelbaum, K., Horos, R., Beckmann, B.M., Strein, C., Davey, N.E., Steinmetz, L.M., Insights into RNA biology from an atlas of mammalian mRNA-binding proteins (2012) Cell, 149, pp. 1393-1406; Ray, D., Kazan, H., Cook, K.B., Weirauch, M.T., Najafabadi, H.S., Li, X., Gueroussov, S., Yang, A., A compendium of RNA-binding motifs for decoding gene regulation (2013) Nature, 499, pp. 172-177; Treiber, T., Treiber, N., Plessmann, U., Harlander, S., Daiss, J.L., Eichner, N., Lehmann, G., Meister, G., A compendium of RNA-binding proteins that regulate MicroRNA biogenesis (2017) Mol Cell, 66, pp. 270-284. , e13; Guardiola-Serrano, F., Haendeler, J., Lukosz, M., Sturm, K., Melchner, H., Altschmied, J., Gene trapping identifies a putative tumor suppressor and a new inducer of cell migration (2008) Biochem Biophys Res Commun, 376, pp. 748-752; Gao, J., Schatton, D., Martinelli, P., Hansen, H., Pla-Martin, D., Barth, E., Becker, C., Sardiello, M., CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins (2014) J Cell Biol, 207, pp. 213-223; Gerber, A.P., Herschlag, D., Brown, P.O., Extensive association of functionally and cytotopically related mRNAs with Puf family RNA-binding proteins in yeast (2004) PLoS Biol, 2; Tu, Y.T., Barrientos, A., The human mitochondrial DEAD-box protein DDX28 resides in RNA granules and functions in mitoribosome assembly (2015) Cell Rep, 10, pp. 854-864; Jourdain, A.A., Koppen, M., Rodley, C.D., Maundrell, K., Gueguen, N., Reynier, P., Guaras, A.M., Simarro, M., A mitochondria-specific isoform of FASTK is present in mitochondrial RNA granules and regulates gene expression and function (2015) Cell Rep, 10, pp. 1110-1121; Popow, J., Alleaume, A.M., Curk, T., Schwarzl, T., Sauer, S., Hentze, M.W., FASTKD2 is an RNA-binding protein required for mitochondrial RNA processing and translation (2015) RNA, 21, pp. 1873-1884; Simarro, M., Gimenez-Cassina, A., Kedersha, N., Lazaro, J.B., Adelmant, G.O., Marto, J.A., Rhee, K., Benarafa, C., Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration (2010) Biochem Biophys Res Commun, 401, pp. 440-446; Antonicka, H., Sasarman, F., Nishimura, T., Paupe, V., Shoubridge, E.A., The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression (2013) Cell Metab, 17, pp. 386-398; Vaux, D.L., Fidler, F., Cumming, G., Replicates and repeats–what is the difference and is it significant? A brief discussion of statistics and experimental design (2012) EMBO Rep, 13, pp. 291-296; Hansen, R.D., Raja, C., Aslani, A., Smith, R.C., Allen, B.J., Determination of skeletal muscle and fat-free mass by nuclear and dual-energy X-ray absorptiometry methods in men and women aged 51–84 y (1–3) (1999) Am J Clin Nutr, 70, pp. 228-233; Norata, G.D., Ongari, M., Garlaschelli, K., Tibolla, G., Grigore, L., Raselli, S., Vettoretti, S., Cefalu, A.B., Effect of the -420C/G variant of the resistin gene promoter on metabolic syndrome, obesity, myocardial infarction and kidney dysfunction (2007) J Intern Med, 262, pp. 104-112; Virbasius, J.V., Scarpulla, R.C., Activation of the human mitochondrial transcription factor A gene by nuclear respiratory factors: a potential regulatory link between nuclear and mitochondrial gene expression in organelle biogenesis (1994) Proc Natl Acad Sci USA, 91, pp. 1309-1313; Shevchenko, A., Tomas, H., Havlis, J., Olsen, J.V., Mann, M., In-gel digestion for mass spectrometric characterization of proteins and proteomes (2007) Nat Protoc, 1, pp. 2856-2860; Rappsilber, J., Mann, M., Ishihama, Y., Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTips (2007) Nat Protoc, 2, pp. 1896-1906; Cox, J., Mann, M., MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification (2008) Nat Biotechnol, 26, pp. 1367-1372; Tyanova, S., Temu, T., Cox, J., The MaxQuant computational platform for mass spectrometry-based shotgun proteomics (2016) Nat Protoc, 11, pp. 2301-2319; Tyanova, S., Temu, T., Sinitcyn, P., Carlson, A., Hein, M.Y., Geiger, T., Mann, M., Cox, J., The Perseus computational platform for comprehensive analysis of (prote)omics data (2016) Nat Methods, 13, pp. 731-740; Dimauro, I., Pearson, T., Caporossi, D., Jackson, M.J., A simple protocol for the subcellular fractionation of skeletal muscle cells and tissue (2012) BMC Res Notes, 5, p. 513; Edgar, R., Domrachev, M., Lash, A.E., Gene Expression Omnibus: NCBI gene expression and hybridization array data repository (2001) Nucleic Acids Res, 30, pp. 207-210; Vizcaino, J.A., Csordas, A., Del-Toro, N., Dianes, J.A., Griss, J., Lavidas, I., Mayer, G., Ternent, T., 2016 update of the PRIDE database and its related tools (2016) Nucleic Acids Res, 44, p. 11033
PY - 2018
Y1 - 2018
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. © 2018 The Authors
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. © 2018 The Authors
KW - functional screens
KW - metabolism
KW - mitochondria
KW - Zc3h10
KW - genomic DNA
KW - glucose
KW - regulator protein
KW - triacylglycerol
KW - unclassified drug
KW - Zinc finger CCCH type containing 10
KW - aged
KW - animal experiment
KW - animal tissue
KW - Article
KW - body mass
KW - cell differentiation
KW - cell isolation
KW - citric acid cycle
KW - controlled study
KW - embryo
KW - fat mass
KW - female
KW - gene overexpression
KW - glucose blood level
KW - homozygote
KW - human
KW - human cell
KW - human tissue
KW - loss of function mutation
KW - male
KW - mitochondrial biogenesis
KW - mitochondrion
KW - mouse
KW - myoblast
KW - myotube
KW - nonhuman
KW - oxygen consumption
KW - peripheral blood mononuclear cell
KW - priority journal
KW - protein depletion
KW - protein expression
KW - protein function
KW - protein subunit
KW - respiratory chain
KW - triacylglycerol blood level
KW - upregulation
M3 - Article
VL - 19
JO - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
IS - 4
ER -