Acknowledgement
This research was supported by the National Key Research and Development Program of China (2019YFA0801402) and the National Natural Science Foundation of China (81971421, 81471485), Shanghai key clinical specialty project (shslczdzk05705), Innovative Research Team of High-Level Local Universities in Shanghai (SHSMU-ZDCX20212200).
References
- Aburawi, E.H. and Souid, A.K. (2012). Lymphocyte respiration in children with Trisomy 21. BMC Pediatr. 12, 193.
- Alafnan, A., Hussain, T., Rizvi, S.M.D., Moin, A., and Alamri, A. (2021). Prostate apoptotic induction and NFκB suppression by dammarolic acid: mechanistic insight into onco-therapeutic action of an aglycone asiaticoside. Curr. Issues Mol. Biol. 43, 932-940. https://doi.org/10.3390/cimb43020066
- Arrazola, M.S., Andraini, T., Szelechowski, M., Mouledous, L., Arnaune-Pelloquin, L., Davezac, N., Belenguer, P., Rampon, C., and Miquel, M.C. (2019). Mitochondria in developmental and adult neurogenesis. Neurotox. Res. 36, 257-267. https://doi.org/10.1007/s12640-018-9942-y
- Beckervordersandforth, R. (2017). Mitochondrial metabolism-mediated regulation of adult neurogenesis. Brain Plast. 3, 73-87. https://doi.org/10.3233/BPL-170044
- Bhatti, J.S., Bhatti, G.K., and Reddy, P.H. (2017). Mitochondrial dysfunction and oxidative stress in metabolic disorders - a step towards mitochondria based therapeutic strategies. Biochim. Biophys. Acta Mol. Basis Dis. 1863, 1066-1077. https://doi.org/10.1016/j.bbadis.2016.11.010
- Bourquin, J.P., Subramanian, A., Langebrake, C., Reinhardt, D., Bernard, O., Ballerini, P., Baruchel, A., Cave, H., Dastugue, N., Hasle, H., et al. (2006). Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling. Proc. Natl. Acad. Sci. U. S. A. 103, 3339-3344. https://doi.org/10.1073/pnas.0511150103
- Concannon, C.G., Tuffy, L.P., Weisova, P., Bonner, H.P., Davila, D., Bonner, C., Devocelle, M.C., Strasser, A., Ward, M.W., and Prehn, J.H. (2010). AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis. J. Cell Biol. 189, 83-94. https://doi.org/10.1083/jcb.200909166
- Coskun, P.E. and Busciglio, J. (2012). Oxidative stress and mitochondrial dysfunction in Down's syndrome: relevance to aging and dementia. Curr. Gerontol. Geriatr. Res. 2012, 383170.
- D'Orsi, B., Mateyka, J., and Prehn, J.H.M. (2017). Control of mitochondrial physiology and cell death by the Bcl-2 family proteins Bax and Bok. Neurochem. Int. 109, 162-170. https://doi.org/10.1016/j.neuint.2017.03.010
- Delabar, J.M., Theophile, D., Rahmani, Z., Chettouh, Z., Blouin, J.L., Prieur, M., Noel, B., and Sinet, P.M. (1993). Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur. J. Hum. Genet. 1, 114-124. https://doi.org/10.1159/000472398
- Edwards, H., Xie, C., LaFiura, K.M., Dombkowski, A.A., Buck, S.A., Boerner, J.L., Taub, J.W., Matherly, L.H., and Ge, Y. (2009). RUNX1 regulates phosphoinositide 3-kinase/AKT pathway: role in chemotherapy sensitivity in acute megakaryocytic leukemia. Blood 114, 2744-2752. https://doi.org/10.1182/blood-2008-09-179812
- El Hajj, N., Dittrich, M., Bock, J., Kraus, T.F., Nanda, I., Muller, T., Seidmann, L., Tralau, T., Galetzka, D., Schneider, E., et al. (2016). Epigenetic dysregulation in the developing Down syndrome cortex. Epigenetics 11, 563-578. https://doi.org/10.1080/15592294.2016.1192736
- Flippo, K.H. and Strack, S. (2017). Mitochondrial dynamics in neuronal injury, development and plasticity. J. Cell Sci. 130, 671-681. https://doi.org/10.1242/jcs.171017
- Grabherr, M.G., Haas, B.J., Yassour, M., Levin, J.Z., Thompson, D.A., Amit, I., Adiconis, X., Fan, L., Raychowdhury, R., Zeng, Q., et al. (2011). Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat. Biotechnol. 29, 644-652. https://doi.org/10.1038/nbt.1883
- Gutti, U., Komati, J.K., Kotipalli, A., Saladi, R.G.V., and Gutti, R.K. (2018). Justicia adhatoda induces megakaryocyte differentiation through mitochondrial ROS generation. Phytomedicine 43, 135-139. https://doi.org/10.1016/j.phymed.2018.04.038
- Halevy, T., Biancotti, J.C., Yanuka, O., Golan-Lev, T., and Benvenisty, N. (2016). Molecular characterization of Down syndrome embryonic stem cells reveals a role for RUNX1 in neural differentiation. Stem Cell Reports 7, 777-786. https://doi.org/10.1016/j.stemcr.2016.08.003
- Hart, J.R. and Vogt, P.K. (2011). Phosphorylation of AKT: a mutational analysis. Oncotarget 2, 467-476. https://doi.org/10.18632/oncotarget.293
- Hirata, K., Nambara, T., Kawatani, K., Nawa, N., Yoshimatsu, H., Kusakabe, H., Banno, K., Nishimura, K., Ohtaka, M., Nakanishi, M., et al. (2020). 4-Phenylbutyrate ameliorates apoptotic neural cell death in Down syndrome by reducing protein aggregates. Sci. Rep. 10, 14047.
- Hu, F. and Liu, F. (2011). Mitochondrial stress: a bridge between mitochondrial dysfunction and metabolic diseases? Cell. Signal. 23, 1528-1533. https://doi.org/10.1016/j.cellsig.2011.05.008
- Izzo, A., Mollo, N., Nitti, M., Paladino, S., Cali, G., Genesio, R., Bonfiglio, F., Cicatiello, R., Barbato, M., Sarnataro, V., et al. (2018). Mitochondrial dysfunction in down syndrome: molecular mechanisms and therapeutic targets. Mol. Med. 24, 2.
- Jia, L., Jiang, Y., Li, X., and Chen, Z. (2020). Purβ promotes hepatic glucose production by increasing Adcy6 transcription. Mol. Metab. 31, 85-97. https://doi.org/10.1016/j.molmet.2019.11.008
- Johnson, J., Mercado-Ayon, E., Mercado-Ayon, Y., Dong, Y.N., Halawani, S., Ngaba, L., and Lynch, D.R. (2021). Mitochondrial dysfunction in the development and progression of neurodegenerative diseases. Arch. Biochem. Biophys. 702, 108698.
- Kann, O. and Kovacs, R. (2007). Mitochondria and neuronal activity. Am. J. Physiol. Cell Physiol. 292, C641-C657. https://doi.org/10.1152/ajpcell.00222.2006
- Laufer, B.I., Hwang, H., Jianu, J.M., Mordaunt, C.E., Korf, I.F., Hertz-Picciotto, I., and LaSalle, J.M. (2021). Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles. Hum. Mol. Genet. 29, 3465-3476. https://doi.org/10.1093/hmg/ddaa218
- Li, H., Liu, J., Wang, Y., Fu, Z., Huttemann, M., Monks, T.J., Chen, A.F., and Wang, J.M. (2017). MiR-27b augments bone marrow progenitor cell survival via suppressing the mitochondrial apoptotic pathway in Type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 313, E391-E401. https://doi.org/10.1152/ajpendo.00073.2017
- Li, X., Sun, Y., Jin, Q., Song, D., and Diao, Y. (2019). Kappa opioid receptor agonists improve postoperative cognitive dysfunction in rats via the JAK2/STAT3 signaling pathway. Int. J. Mol. Med. 44, 1866-1876. https://doi.org/10.3892/ijmm.2019.4339
- Li, Z., Jiang, T., Lu, Q., Xu, K., He, J., Xie, L., Chen, Z., Zheng, Z., Ye, L., Xu, K., et al. (2020). Berberine attenuated the cytotoxicity induced by t-BHP via inhibiting oxidative stress and mitochondria dysfunction in PC-12 cells. Cell. Mol. Neurobiol. 40, 587-602. https://doi.org/10.1007/s10571-019-00756-7
- Lim, H.J., Crowe, P., and Yang, J.L. (2015). Current clinical regulation of PI3K/PTEN/Akt/mTOR signalling in treatment of human cancer. J. Cancer Res. Clin. Oncol. 141, 671-689. https://doi.org/10.1007/s00432-014-1803-3
- Liu, S., Zhang, Y., Huang, C., and Lin, S. (2020). miR-215-5p is an anticancer gene in multiple myeloma by targeting RUNX1 and deactivating the PI3K/AKT/mTOR pathway. J. Cell. Biochem. 121, 1475-1490. https://doi.org/10.1002/jcb.29383
- Lv, J., Liang, Y., Tu, Y., Chen, J., and Xie, Y. (2018). Hypoxic preconditioning reduces propofol-induced neuroapoptosis via regulation of Bcl-2 and Bax and downregulation of activated caspase-3 in the hippocampus of neonatal rats. Neurol. Res. 40, 767-773. https://doi.org/10.1080/01616412.2018.1477545
- McCubrey, J.A., Steelman, L.S., Chappell, W.H., Abrams, S.L., Montalto, G., Cervello, M., Nicoletti, F., Fagone, P., Malaponte, G., Mazzarino, M.C., et al. (2012). Mutations and deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades which alter therapy response. Oncotarget 3, 954-987. https://doi.org/10.18632/oncotarget.652
- Nishimura, A., Hirabayashi, S., Hasegawa, D., Yoshida, K., Shiraishi, Y., Ashiarai, M., Hosoya, Y., Fujiwara, T., Harigae, H., Miyano, S., et al. (2021). Acquisition of monosomy 7 and a RUNX1 mutation in Pearson syndrome. Pediatr. Blood Cancer 68, e28799.
- Ohnishi, T., Ohnishi, S.T., and Salerno, J.C. (2018). Five decades of research on mitochondrial NADH-quinone oxidoreductase (complex I). Biol. Chem. 399, 1249-1264. https://doi.org/10.1515/hsz-2018-0164
- Pardo, M., Cheng, Y., Sitbon, Y.H., Lowell, J.A., Grieco, S.F., Worthen, R.J., Desse, S., and Barreda-Diaz, A. (2019). Insulin growth factor 2 (IGF2) as an emergent target in psychiatric and neurological disorders. Review. Neurosci. Res. 149, 1-13. https://doi.org/10.1016/j.neures.2018.10.012
- Patel, A., Rees, S.D., Kelly, M.A., Bain, S.C., Barnett, A.H., Thalitaya, D., and Prasher, V.P. (2011). Association of variants within APOE, SORL1, RUNX1, BACE1 and ALDH18A1 with dementia in Alzheimer's disease in subjects with Down syndrome. Neurosci. Lett. 487, 144-148. https://doi.org/10.1016/j.neulet.2010.10.010
- Pecze, L. and Szabo, C. (2021). Meta-analysis of gene expression patterns in Down syndrome highlights significant alterations in mitochondrial and bioenergetic pathways. Mitochondrion 57, 163-172. https://doi.org/10.1016/j.mito.2020.12.017
- Pelleri, M.C., Cicchini, E., Locatelli, C., Vitale, L., Caracausi, M., Piovesan, A., Rocca, A., Po-letti, G., Seri, M., Strippoli, P., et al. (2016). Systematic reanalysis of partial trisomy 21 cases with or without Down syndrome suggests a small region on 21q22.13 as critical to the phenotype. Hum. Mol. Genet. 25, 2525-2538. https://doi.org/10.1093/hmg/ddw116
- Perluigi, M., Pupo, G., Tramutola, A., Cini, C., Coccia, R., Barone, E., Head, E., Butterfield, D.A., and Di Domenico, F. (2014). Neuropathological role of PI3K/Akt/mTOR axis in Down syndrome brain. Biochim. Biophys. Acta 1842, 1144-1153. https://doi.org/10.1016/j.bbadis.2014.04.007
- Putcha, G.V., Moulder, K.L., Golden, J.P., Bouillet, P., Adams, J.A., Strasser, A., and Johnson, E.M. (2001). Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis. Neuron 29, 615-628. https://doi.org/10.1016/S0896-6273(01)00238-0
- Qiu, J.J., Liu, Y.N., Ren, Z.R., and Yan, J.B. (2017). Dysfunctions of mitochondria in close association with strong perturbation of long noncoding RNAs expression in down syndrome. Int. J. Biochem. Cell Biol. 92, 115-120. https://doi.org/10.1016/j.biocel.2017.09.017
- Salemi, M., Giambirtone, M., Barone, C., Salluzzo, M.G., Russo, R., Giudice, M.L., Cutuli, S., Ridolfo, F., and Romano, C. (2018). Mitochondrial mRNA expression in fibroblasts of Down syndrome subjects. Hum. Cell 31, 179-181. https://doi.org/10.1007/s13577-018-0205-2
- Salemi, M., Ridolfo, F., Salluzzo, M.G., Cannarrella, R., Giambirtone, M., Caniglia, S., Tirolo, C., Ferri, R., and Romano, C. (2020). Humanin gene expression in fibroblast of Down syndrome subjects. Int. J. Med. Sci. 17, 320-324. https://doi.org/10.7150/ijms.39145
- Shah, S.I., Paine, J.G., Perez, C., and Ullah, G. (2019). Mitochondrial fragmentation and network architecture in degenerative diseases. PLoS One 14, e0223014.
- Shin, J., Shim, H.G., Hwang, T., Kim, H., Kang, S.H., Dho, Y.S., Park, S.H., Kim, S.J., and Park, C.K. (2017). Restoration of miR-29b exerts anti-cancer effects on glioblastoma. Cancer Cell Int. 17, 104.
- Vacca, R.A., Bawari, S., Valenti, D., Tewari, D., Nabavi, S.F., Shirooie, S., Sah, A.N., Volpicella, M., Braidy, N., and Nabavi, S.M. (2019). Down syndrome: neurobiological alterations and therapeutic targets. Neurosci. Biobehav. Rev. 98, 234-255. https://doi.org/10.1016/j.neubiorev.2019.01.001
- Valenti, D., Braidy, N., De Rasmo, D., Signorile, A., Rossi, L., Atanasov, A.G., Volpicella, M., Henrion-Caude, A., Nabavi, S.M., and Vacca, R.A. (2018). Mitochondria as pharmacological targets in Down syndrome. Free Radic. Biol. Med. 114, 69-83. https://doi.org/10.1016/j.freeradbiomed.2017.08.014
- Valiyari, S., Salami, M., Mahdian, R., Shokrgozar, M.A., Oloomi, M., Mohammadi Farsani, A., and Bouzari, S. (2017). sIL-24 peptide, a human interleukin-24 isoform, induces mitochondrial-mediated apoptosis in human cancer cells. Cancer Chemother. Pharmacol. 80, 451-459. https://doi.org/10.1007/s00280-017-3370-1
- Wong, R.S. (2011). Apoptosis in cancer: from pathogenesis to treatment. J. Exp. Clin. Cancer Res. 30, 87.
- Wu, J., Zheng, C., Wang, X., Yun, S., Zhao, Y., Liu, L., Lu, Y., Ye, Y., Zhu, X., Zhang, C., et al. (2015). MicroRNA-30 family members regulate calcium/calcineurin signaling in podocytes. J. Clin. Invest. 125, 4091-4106. https://doi.org/10.1172/JCI81061
- Ye, Z., Xia, P., Cheng, Z.G., and Guo, Q. (2015). Neuroprotection induced by sevoflurane-delayed post-conditioning is attributable to increased phosphorylation of mitochondrial GSK-3β through the PI3K/Akt survival pathway. J. Neurol. Sci. 348, 216-225. https://doi.org/10.1016/j.jns.2014.12.011
- Yoshikawa, M., Hirabayashi, M., Ito, R., Ozaki, S., Aizawa, S., Masuda, T., Senzaki, K., and Shiga, T. (2015). Contribution of the Runx1 transcription factor to axonal pathfinding and muscle innervation by hypoglossal motoneurons. Dev. Neurobiol. 75, 1295-1314. https://doi.org/10.1002/dneu.22285
- Yoshikawa, M., Masuda, T., Kobayashi, A., Senzaki, K., Ozaki, S., Aizawa, S., and Shiga, T. (2016). Runx1 contributes to the functional switching of bone morphogenetic protein 4 (BMP4) from neurite outgrowth promoting to suppressing in dorsal root ganglion. Mol. Cell. Neurosci. 72, 114-122. https://doi.org/10.1016/j.mcn.2016.02.001
- Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C., Zhou, H., Jiang, X., Liu, Q., and Meng, F. (2016). Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway. Oncol. Rep. 36, 1626-1632. https://doi.org/10.3892/or.2016.4963
- Yu, M., Du, G., Xu, Q., Huang, Z., Huang, X., Qin, Y., Han, L., Fan, Y., Zhang, Y., Han, X., et al. (2018). Integrated analysis of DNA methylome and transcriptome identified CREB5 as a novel risk gene contributing to recurrent pregnancy loss. EBioMedicine 35, 334-344. https://doi.org/10.1016/j.ebiom.2018.07.042
- Yuan, Y., Chen, Y., Peng, T., Li, L., Zhu, W., Liu, F., Liu, S., An, X., Luo, R., Cheng, J., et al. (2019). Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition. Clin. Sci. (Lond.) 133, 1759-1777. https://doi.org/10.1042/CS20190672
- Zamponi, E. and Helguera, P.R. (2019). The shape of mitochondrial dysfunction in Down syndrome. Dev. Neurobiol. 79, 613-621. https://doi.org/10.1002/dneu.22673
- Zhang, W., Hu, X., Shen, Q., and Xing, D. (2019). Mitochondria-specific drug release and reactive oxygen species burst induced by polyprodrug nanoreactors can enhance chemotherapy. Nat. Commun. 10, 1704.
- Zhao, X., Song, X., Bai, X., Fei, N., Huang, Y., Zhao, Z., Du, Q., Zhang, H., Zhang, L., and Tong, D. (2016). miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1). PeerJ 4, e1635.