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MicroRNA-210 Controls Mitochondrial Metabolism during Hypoxia by Repressing the Iron-Sulfur Cluster Assembly Proteins ISCU1/2
Open accessAbstract
Repression of mitochondrial respiration represents an evolutionarily ancient cellular adaptation to hypoxia and profoundly influences cell survival and function; however, the underlying molecular mechanisms are incompletely understood. Primarily utilizing pulmonary arterial endothelial cells as a representative hypoxic cell type, we identify the iron-sulfur cluster assembly proteins (ISCU1/2) as direct targets for repression by the hypoxia-induced microRNA-210 (miR-210). ISCU1/2 facilitate the assembly of iron-sulfur clusters, prosthetic groups that are critical for electron transport and mitochondrial oxidation-reduction reactions. Under in vivo conditions of upregulating miR-210 and repressing ISCU1/2, the integrity of iron-sulfur clusters is disrupted. In turn, by repressing ISCU1/2 during hypoxia, miR-210 decreases the activity of prototypical iron-sulfur proteins controlling mitochondrial metabolism, including Complex I and aconitase. Consequently, miR-210 represses mitochondrial respiration and associated downstream functions. These results identify important mechanistic connections among microRNA, iron-sulfur cluster biology, hypoxia, and mitochondrial function, with broad implications for cellular metabolism and adaptation to cellular stress.
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“The coordinate metabolic changes caused by HIF-1 that alter mitochondrial function are attributable, in part, to the HIF-1-mediated transcriptional upregulation of microRNA 210 (miR210), which specifically inhibits Fe-S complex formation to alter mitochondrial bioenergetics and ROS production (Pasteur effect) (69).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [69]
In the citing paper
“Interestingly, during normoxia, forced expression of miR210 caused an increase in ROS generation (69, 81), possibly due to deficiencies in complex I that may promote electron leak in the presence of molecular oxygen.”
From Redox regulation of mitochondrial function (2012) · cites this paper as [69]
In the citing paper
“Nonetheless, experimental evidence suggests that enhanced ROS production is not a sustained event in hypoxia (69, 385).”
From Redox regulation of mitochondrial function (2012) · cites this paper as [69]
In the citing paper
“Within mitochondria it targets regulatory proteins that assist in the assembly of the complexes of the electron transport chain, and suppresses respiration (103, 108).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [103]
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1 retracted
Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., Gonzalez, F. J., & Semenza, G. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800102200 · Cited by 1,601 · cited 1×
“Mitophagy has been characterized as a HIF-dependent mechanism (Zhang et al., 2008).”
BackgroundRetractedKim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905 · cited 1×
“First, by induction of PDK1, HIF-1a decreases the activity of the TCA cycle, increases glycolysis, and reduces mitochondrial electron flux (Kim et al., 2006).”
Iron-sulfur clusters: nature's modular, multipurpose structures
Beinert, H., Holm, R. H., & Münck, E. (1997) · Science · doi:10.1126/science.277.5326.653 · Cited by 1,944 · cited 4×
“280 Cell Metabolism 10, 273–284, October 7, 2009 ª2009 Elsevier Inc. to oxidative stress (Beinert et al., 1997), along with repression of iron-sulfur cluster biogenesis via downregulated ISCU1/2, may provide a real-time redox-sensitive ‘‘switch’’ that is triggered by hypoxia to induce downstream…”
InfluentialHIF-1 Regulates Cytochrome Oxidase Subunits to Optimize Efficiency of Respiration in Hypoxic Cells
Fukuda, R., Zhang, H., Kim, J.-W., Shimoda, L., Dang, C. V., & Semenza, G. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.047 · Cited by 1,225 · cited 1×
“Second, HIF-1a induces a COX4-1 to COX4-2 subunit switch during hypoxia to improve the efficiency of electron transfer to oxygen at Complex IV (Fukuda et al., 2007).”
Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1
Manalo, D. J., Rowan, A., Lavoie, T., Natarajan, L., Kelly, B. D., Ye, S. Q., Garcia, J. G. N., & Semenza, G. L. (2005) · Blood · doi:10.1182/blood-2004-07-2958 · Cited by 1,154 · cited 1×
“Conditions were based on studies of hypoxic exposure of HPAECs (Manalo et al., 2005) to allow for steady-state adaptation without nonspecific cell death.”
A MicroRNA Signature of Hypoxia
Kulshreshtha, R., Ferracin, M., Wojcik, S. E., Garzon, R., Alder, H., Agosto-Perez, F. J., Davuluri, R., Liu, C.-G., Croce, C. M., Negrini, M., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01395-06 · Cited by 1,055 · cited 5×
“…with other studies demonstrating the repression of apoptosis by miR-210 during hypoxia in other cellular contexts (Fasanaro et al., 2008; Kulshreshtha et al., 2007), these data lend credence to a model in which miR-210 carries a maladaptive role during normoxia, causing a mismatch of…”
InfluentialHypoxia-Induced Pulmonary Vascular Remodeling
Stenmark, K. R., Fagan, K. A., & Frid, M. G. (2006) · Circulation Research · doi:10.1161/01.res.0000243584.45145.3f · Cited by 1,001 · cited 2×
“In particular, this response may be especially important to the pulmonary vascular endothelium, which directly responds to hypoxia by controlling the release of vasoactive effectors, thereby critically influencing normal vascular physiology and the development of pulmonary hypertension (Stenmark et al., 2006).”
Fasanaro, P., D'Alessandra, Y., Di Stefano, V., Melchionna, R., Romani, S., Pompilio, G., Capogrossi, M. C., & Martelli, F. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800731200 · Cited by 912 · cited 6×
“Some, but not all, of these miRNA have been identified in other transformed (Kulshreshtha et al., 2007) or primary endothelial cells (Fasanaro et al., 2008) exposed to hypoxia.”
Influentialhsa-miR-210 Is Induced by Hypoxia and Is an Independent Prognostic Factor in Breast Cancer
Camps, C., Buffa, F. M., Colella, S., Moore, J., Sotiriou, C. P., Sheldon, H., Harris, A. L., Gleadle, J., & Ragoussis, J. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1755 · Cited by 672 · cited 3×
“Additionally, miR-210 is specifically induced by HIF-1a but not HIF-2a (Camps et al., 2008), a second transcriptional regulator of the hypoxic response, which carries partial but not full redundancy in function with HIF-1a (Wang et al., 2005).”
Transcription Factor HIF-1 Is a Necessary Mediator of the Pasteur Effect in Mammalian Cells
Seagroves, T. N., Ryan, H. E., Lu, H., Wouters, B. G., Knapp, M., Thibault, P., Laderoute, K. R., & Johnson, R. S. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.10.3436-3444.2001 · Cited by 634 · cited 4×
“The elucidation of the miR-210-ISCU1/2 regulatory pathway substantially clarifies the nature of the complex crosstalk between HIF-1a and mitochondria (Seagroves et al., 2001) and complements other HIF-dependent processes proposed to regulate the mismatch of reduced oxygen tension and mitochondrial electron transport.”
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Gileles‐Hillel, A., Bhattacharjee, R., Gorelik, M., & Narang, I. (2024) · Clinics in Chest Medicine · doi:10.1016/j.ccm.2024.03.004 · Cited by 25
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Patella, F., & Rainaldi, G. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0775-6 · Cited by 23
“ISCU1/2 COX10 Inhibition of mitochondrial respiration Human ECs (HPAEC, HUVEC, HAEC), colon cancer cell lines [ 37 , 39]”
BackgroundMethodThe Role of miR-210 in the Biological System: A Current Overview
Xu, H., Al-Ward, H., Shaher, F., Liu, C., & Liu, N. (2019) · Human Heredity · doi:10.1159/000509280 · Cited by 25
Tan, W. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i46.13030 · Cited by 22
Lin, M.-Y., Chang, Y., Wang, S.-Y., Yang, M., Chang, C.-H., Hsiao, M., Kitsis, R. N., & Lee, Y. (2021) · Antioxidants · doi:10.3390/antiox10111808 · Cited by 23
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Environmental and behavioral regulation of HIF-mitochondria crosstalk
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“The data suggest a metabolic shift from oxidative phosphorylation to glycolysis, which is in line with the HIF-1 activity that stimulates the glycolytic genes while suppressing the TCA cycle genes (5, 11, 12).”
BackgroundTakahashi, E., & Sato, M. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00255.2013 · Cited by 22
Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets
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“In addition, ETC complex I requires iron-sulfur cluster assembly assisted by iron-sulfur cluster assembly protein 1/2 (ISCU1/2), but hypoxia-induced HIF1α increases miR-210 expression, which targets ISCU1/2 mRNA and inhibits its expression, resulting in decreased complex I activity (Chan et al., 2009).”
BackgroundOxidative Stress and Inflammation in Uterine–Vascular Adaptation During Pregnancy
Mandalà, M. (2025) · Antioxidants · doi:10.3390/antiox14091051 · Cited by 21
Defective mitochondrial quality control in the aging of skeletal muscle
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“All these genes mediate the effects of miR-210 participating in oxidative stress and mitochondrial metabolism, angiogenesis [42], cell survival [43], DNA repair [10], and cell migration and invasion [30].”
BackgroundThe Role of MicroRNAs in Lung Cancer Metabolism
Azizi, M. I. H. N., Othman, I., & Naidu, R. (2021) · Cancers · doi:10.3390/cancers13071716 · Cited by 22
“Previous studies have shown miR-210 involvement in ISCU1/2, which is responsible for integrating iron-sulfur clusters into the enzymes involved in energy production via the TCA cycle and contributing to ETC activity [101].”
BackgroundPang, Y., Tan, G., Yang, X., Lin, Y., Chen, Y., Zhang, J., Xie, T., Zhou, H., Fang, J. Q., Zhao, Q., et al. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02131-3 · Cited by 21
“Discussion Differential expression of the proteins required for ISC biosynthesis has been reported to be implications for cellular metabolism and adaptation to cellular stress [22, 42].”
BackgroundLi, Y., Song, R., Shen, G., Huang, L., Xiao, D., Ma, Q., & Zhang, L. (2023) · Stroke · doi:10.1161/strokeaha.122.041651 · Cited by 21
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Duan, X., Yang, Y., Zhang, H., Liu, B., Wei, W., Wang, L., Sun, C., Yao, W., Cui, L., Zhou, X., et al. (2019) · Chemosphere · doi:10.1016/j.chemosphere.2019.125773 · Cited by 22
MicroRNA-101-3p Modulates Mitochondrial Metabolism via the Regulation of Complex II Assembly
Ziemann, M., Lim, S. C., Kang, Y., Samuel, S., Sanchez, M. I. G. L., Gantier, M. P., Stojanovski, D., & McKenzie, M. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167361 · Cited by 23
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Poredoš, P., Šabovič, M., Mijovski, M. B., Starčević, J. N., Antignani, P. L., Paraskevas, K. I., Mikhailidis, D. P., & Blinc, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231912054 · Cited by 23
Hypoxic State of Cells and Immunosenescence: A Focus on the Role of the HIF Signaling Pathway
Troise, D. E., Infante, B., Mercuri, S., Netti, G. S., Ranieri, E., Gesualdo, L., Stallone, G., & Pontrelli, P. (2023) · Biomedicines · doi:10.3390/biomedicines11082163 · Cited by 22
“Contrarily, in order to decrease the generation of reactive oxygen species (ROS) under prolonged hypoxia, the activity of the I, II, and III ETC complexes is reduced.”
BackgroundThe Janus face of HIF-1α in ischemic stroke and the possible associated pathways
Amin, N., Abbasi, I. N., Wu, F., Shi, Z., Sundus, J., Badry, A., Yuan, X., Zhao, B., Pan, J., Mi, X., et al. (2024) · Neurochemistry International · doi:10.1016/j.neuint.2024.105747 · Cited by 23
Hypoxamirs in Pulmonary Hypertension: Breathing New Life into Pulmonary Vascular Research.
Hale, A., White, K., & Chan, S. Y. (2012) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2223-3652.2012.08.01 · Cited by 21
“The actions of miR-210 in PH could be linked to down-regulation of the iron sulfur complex assembly proteins 1/2 (ISCU1/2) (70) and additional mitochondrial electron transport proteins (71,72) which repress mitochondrial metabolism in favor of glycolysis for energy production.”
BackgroundSelf-citationZhang, H., Liang, F., Yue, J., Liu, P., Wang, J., Wang, Z., Li, H., Cheng, D., Du, J., Zhang, K., et al. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.5064 · Cited by 20
“MicroRNAs are abnormally expressed when exposed to hypoxia, lipopolysaccharides or tumor necrosis factor-α (23,24).”
BackgroundHIF-1α and growth plate development: what we really know
Schipani, E., Mangiavini, L., & Merceron, C. (2015) · BoneKEy Reports · doi:10.1038/bonekey.2015.99 · Cited by 21
HypoxamiRs: the hidden architects of tissue adaptation in hypoxia
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“In a manner similar to conventional genes, HIF-1 α directly binds to an HRE located on the proximal promoter of miR-210 [15].”
LI, X.-Y., FENG, X.-Z., Tang, J., Dong, K., Wang, J., MENG, C.-C., Wang, J., Yi-wo, M., & Sun, Z. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.4995 · Cited by 19
Yang, J., Hao, J., Lin, Y., Guo, Y., Liao, K., Yang, M., Cheng, H., Yang, M., & Chen, K. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.810974 · Cited by 19
Tian, L., Chen, J., Chen, M., Gui, C., Zhong, C., Hong, L., Xie, C., Wu, X., Yang, L., Ahmad, V., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.589093 · Cited by 19
“Under hypoxia, microRNA-210 represses the expression of IscU1/2 and affects mitochondrial metabolism by repressing aconitase and complex I activity (11, 16, 17).”
BackgroundMethodSalloum, Z., Lehoux, E. A., Harper, M., & Catelas, I. (2020) · Journal of Orthopaedic Research® · doi:10.1002/jor.24758 · Cited by 19
Epigenetic reprogramming of mtDNA and its etiology in mitochondrial diseases
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“…miR-210 is overexpressed in hypoxic conditions and targets Iron-sulfur cluster assembly proteins 1 & 2 (ISCU1/2) like NDUFS , succinate dehydrogenase subunit D and cytochrome c oxidase assembly protein of CI (complex I), resulting in dysregulation of mitochondrial redox reaction and ETC [57, 58].”
A Primer on the Role of MicroRNAs in Endothelial Biology and Vascular Disease
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Infante‐Menéndez, J., López‐Pastor, A. R., González‐López, P., Gómez‐Hernández, A., & Escribano, Ó. (2020) · Antioxidants · doi:10.3390/antiox9070607 · Cited by 19
“Considering iron metabolism, in response to hypoxia, the inhibition of iron-sulfur cluster assembly enzymes 1/2 (ISCU1/2) is mediated by miR-210.”
BackgroundPang, Y., Lin, Y., Wang, X., Wang, J., Liu, Q., Ding, N., Huang, L., Xiang, Q., Fang, J. Q., Tan, G., et al. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174844 · Cited by 18
El‐Gowelli, H. M., Saad, E. I., Abdel‐Galil, A. A., & Ibrahim, E. R. (2015) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2015.08.002 · Cited by 19
A microRNA Link to Glioblastoma Heterogeneity
Singh, S. K., Vartanian, A., Burrell, K. E., & Zadeh, G. M. (2012) · Cancers · doi:10.3390/cancers4030846 · Cited by 19
“assembly proteins ISCU1/2 [133].”
MicroRNA-210 and its theranostic potential
Ren, C.-X., Leng, R., Fan, Y., Pan, H., Wu, C., & Ye, D. (2016) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2016.1206890 · Cited by 18
“Moreover, miR-210 controls mitochondrial function by repressing multiple related mitochondrial targets in various cell lines, such as iron–sulfur cluster scaffold homolog1/2 (ISCU1/2) [65] and cytochrome–coxidase assembly protein [19].”
BackgroundChang, T., Chen, Y.-J., Luo, J., Zhang, C., Chen, S.-Y., Lin, Z.-Q., Zhang, P., Shen, Y., Tang, T.-X., Li, H., et al. (2025) · ImmunoTargets and Therapy · doi:10.2147/itt.s492334 · Cited by 18
“65 Additionally, mir-210 has been demonstrated to suppress the expression of NDUFA4, succinate dehydrogenase complex subunit D (SDHD), and COX10, which are crucial components in the formation and assembly of ETC-associated complexes (Figure 3B).”
Integrating epigenetics and metabolomics to advance treatments for pulmonary arterial hypertension
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Loss of miR-210 leads to progressive retinal degeneration inDrosophila melanogaster
Weigelt, C. M., Hahn, O., Arlt, K., Gruhn, M., Jahn, A. J., Eßer, J., Werner, J. A., Klein, C., Büschges, A., Grönke, S., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201800149 · Cited by 16
“…miRNAs, including the highly evolutionarily conserved miR-210. miR-210 has been intensively studied in the context of the response to hypoxia in mammalian cell culture (Camps et al, 2008; Fasanaro et al, 2008; Giannakakis et al, 2008; Pulkkinen et al, 2008; Chan et al, 2009; Huang et al, 2009).”
BackgroundPranzini, E., Leo, A., Rapizzi, E., Ramazzotti, M., Magherini, F., Giovannelli, L., Caselli, A., Cirri, P., Taddei, M. L., & Paoli, P. (2019) · Molecular Carcinogenesis · doi:10.1002/mc.23107 · Cited by 17
“Coherently, miR‐210‐3p modulation also impacts on different steps of mitochondrial metabolism, affecting activity of the ETC complexes.(19,20) Subunit D of mitochondrial succinate dehydrogenase complex (SDHD) is a known target of miR‐210‐3p.”
Nakada, C., Hijiya, N., Tsukamoto, Y., Yano, S., Kai, T., Uchida, T., Kimoto, M., Takahashi, M., Daa, T., Matsuura, K., et al. (2020) · The Journal of Pathology · doi:10.1002/path.5394 · Cited by 17
“Indeed, it has been reported that ectopically expressed miR-210 decreases the mitochondrial respiration rate by acting on respiration complex II and complex I + II in OxPhos [39] and that ectopic expression of miR-210 suppresses complex I activity [34,36].”
BackgroundFrataxin and endothelial cell senescence in pulmonary hypertension
Lawrie, A., & Francis, S. (2021) · Journal of Clinical Investigation · doi:10.1172/jci149721 · Cited by 17
Parikh, V. N., Park, J., Nikolić, I., Channick, R. N., Yu, P. B., Marco, T. D., Hsue, P. Y., & Chan, S. Y. (2015) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000000741 · Cited by 17
Self-citationThe insights into molecular pathways of hypoxia‐inducible factor in the brain
Ostrowski, R. P., & Zhang, J. H. (2018) · Journal of Neuroscience Research · doi:10.1002/jnr.24366 · Cited by 17
“…2006), and the activation of Bcl‐2 13‐KDa interacting protein 3 (BNIP3), which triggers mitochondrial selective autophagy; while the induc‐ tion of miR‐210 represses the iron–sulfur cluster assembly proteins, important for the function of complex I and aconitase (Chan et al., 2009; Semenza, 2011).”
BackgroundCanale, P., & Borghini, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126620 · Cited by 9
“…a hypoxia-induced miRNA, suppresses the expression of iron-sulfur cluster homolog (ISCU1/2), impairing mitochondrial respiration and ROS generation [96]. miRNA-210 also suppresses mitochondrial function by targeting the 3 ′ UTR of mitochondrial proteins, including mitochondrial ISCU, COX10,…”
BackgroundmiR-210 in ischaemic stroke: biomarker potential, challenges and future perspectives
Aderinto, N., Olatunji, G. D., Kokori, E., Sanker, V., Yusuf, I. A., Oluwakorede, A. T., Egbunu, E. O., Aboje, J. E., Apampa, O. O., Ogieuhi, I. J., et al. (2024) · European journal of medical research · doi:10.1186/s40001-024-02029-6 · Cited by 16
“[11, 12, 46, 53, 57–62] et al. demonstrated that miR-210 upregulation induced pro-apoptotic gene caspase-3 expression, contributing to endothelial cell apoptosis [59].”
BackgroundMicroRNAs and mesenchymal stem cells: hope for pulmonary hypertension
Zhu, Z., Fang, Z., Hu, X., & Zhou, S. (2015) · Brazilian Journal of Cardiovascular Surgery · doi:10.5935/1678-9741.20150033 · Cited by 16
“Previously study performed on pulmonary artery endothelial cells (PAECs) found that miR-210 can provide an adaptation to hypoxic conditions by targeting Iron-Sulfur Cluster Assembly Proteins 1/2 (ISCU) [30] .”
BackgroundMicroRNA‐210 is increased and it is required for dedifferentiation of osteosarcoma cell line
Zhang, H., Mai, Q., & Chen, J. (2016) · Cell Biology International · doi:10.1002/cbin.10721 · Cited by 16
“, 2015), and mitochondrial metabolism (Chan et al., 2009; Chen et al., 2010; White et al., 2015), in many kinds of tumors.”
BackgroundSong, Y., Hu, B., Xu, L. Z., Liu, J.-Q., Chen, X., Zheng, Y., Chen, M., Wang, J., Sun, R.-H., & Mo, S. (2019) · Experimental Cell Research · doi:10.1016/j.yexcr.2019.03.004 · Cited by 16
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“, 2007), and mitochondrial respiration (Chan et al., 2009).”
Lin, K., Ng, S., Paul, C. R., Chen, H., Zeng, R., Liu, J., Padma, V. V., Huang, C., & Kuo, W. (2021) · Journal of Cellular Biochemistry · doi:10.1002/jcb.30146 · Cited by 15
“53–56 miR‐210 has been reported as a hypoxia‐sensitive miRNA, and its overexpression can protect cardiac cells from hypoxia‐ induced apoptosis.(57) Furthermore, two important factors, iron‐sulfur cluster scaffold homolog and cytochrome c oxidase assembly protein (COX10), which are involved in the mitochondrial electro…”
BackgroundYin, H., Liu, Y., Dong, Q., Wang, H., Yan, Y., Wang, X., Wan, X., Yuan, G., & Pan, Y. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216862 · Cited by 16
Potential roles of microRNAs in redox state: An update
Yaribeygi, H., Atkin, S. L., & Sahebkar, A. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.27475 · Cited by 15
“It was suggested that miR‐210 was also able to suppress the mitochondrial respiratory chain and could trigger related down‐stream processes by downregulation of ISCU1/2 (iron‐sulfur cluster assembly proteins) during hypoxia.(43) Mitochondria have their own type of miRs (such as miR‐302a) that are important factors in…”
BackgroundOrchestration of lincRNA-p21 and miR-155 in Modulating the Adaptive Dynamics of HIF-1α
Sun, C., Zhang, X., Liu, F., & Wang, W. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00871 · Cited by 15
“For example, HIF-1-targeted miR-210 is shown to regulate cellular metabolism or angiogenesis during hypoxia (Chan et al., 2009; Li et al., 2016).”
Marwarha, G., Rosand, O., Scrimgeour, N., Slagsvold, K. H., & Høydal, M. (2021) · Biomedicines · doi:10.3390/biomedicines10010042 · Cited by 13
Zhang, W., Zhang, S., Li, B., Sun, M., & Zhang, J. (2018) · BMC Anesthesiology · doi:10.1186/s12871-018-0532-6 · Cited by 14
“Recent studies have investigated the repression of miRNA-210 on iron-sulfur cluster (ISC) assembly proteins, and ISCU2 was predicted to contain a highly conserved binding site for miRNA-210 [26, 27].”
BackgroundHypoxia-Inducible Factors and Burn-Associated Acute Kidney Injury—A New Paradigm?
Enescu, D. M., Parasca, S. V., Bădoiu, S. C., Miricescu, D., Totan, A., Stănescu-Spînu, I.-I., Greabu, M., & Jinga, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052470 · Cited by 17
Hypoxia-induced pulmonary hypertension in adults and newborns: implications for drug development
Ahmed, A. S. I., Blood, A. B., & Zhang, L. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.104015 · Cited by 13
Luo, J., Zhang, X., Liang, Z., Zhuang, W., Jiang, M., Ma, M., Peng, S., Huang, S., Qiao, G., & Chen, Q. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07787-7 · Cited by 14
“ISCU is known to play a crucial role in the assembly and maintenance of iron-sulfur clusters, which are essential cofactors for a wide range of proteins involved in various biological processes [11, 12].”
Hu, H., Ding, Y., Wang, Y., Geng, S., Liu, J., He, J., Yang, L., Li, X., Yuan, M., Zhu, S., et al. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.5322 · Cited by 14
“As a downstream target of miR-210 (12,33,35), ISCU is responsible for the assembly of iron sulfur clusters [Fe-S] in mitochondrial respiratory complexes (complexes I, II and III) (21,36).”
Fuhrmann, D. C., & Brüne, B. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04146-z · Cited by 15
MicroRNA Target Identification: Lessons from HypoxamiRs
Bertero, T., Robbe-Sermesant, K., Lebrigand, K., Ponzio, G., Pottier, N., Rezzonico, R., Mazure, N. M., Barbry, P., & Mari, B. P. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5648 · Cited by 14
“Similarly, combining in silico prediction algorithms and gene annotation tools led to the identification of an additional central target for miR-210, ISCU1/2, which is closely associated with mitochondria metabolism (31, 34, 58).”
Subcellular Energetics and Metabolism: A Cross-Species Framework
Thiele, R. H. (2017) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000001773 · Cited by 14
Differentially Expressed miRNAs Influence Metabolic Processes in Pituitary Oncocytoma
Krokker, L., Nyírő, G., Reiniger, L., Darvasi, O., Szücs, N., Czirják, S., Tóth, M., Igaz, P., Patócs, A., & Butz, H. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02789-2 · Cited by 14
Hypoxia-Induced Changes in Endothelial Cell Phenotype and Function
Tóth, A., & Jeney, V. (2025) · Antioxidants and Redox Signaling · doi:10.1089/ars.2025.1022 · Cited by 14
“Hypoxia-induced increase in miR-210 and downregulation of ISCU1/2 lead to impaired Fe-S cluster integrity, repression of mitochondrial metabolism, and increased ROS production.”
InfluentialLiapopoulos, D., Sarantis, P., Biniari, T., Bousou, T.-E., Trifylli, E.-M., Anastasiou, I. A., Kokkali, S., Korakaki, D., Pantzios, S., Koustas, E., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13092243 · Cited by 13
“Hypoxia adds a second layer: miR-210 and miR-1307-3p (both HIF-induced) inhibit electron-transport components and enforce AKT/mTOR signaling, respectively, locking cells into glycolysis, while creating a positive feedback to stabilize HIF-1 α [29,35].”
MicroRNA‐210‐mediated mtROS confer hypoxia‐induced suppression of STOCs in ovine uterine arteries
Hu, X., Song, R., Dasgupta, C., Romero, M., Juarez, R., Hanson, J., Blood, A. B., Wilson, S. M., & Zhang, L. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15914 · Cited by 13
Marwarha, G., Røsand, Ø., Slagsvold, K. H., & Høydal, M. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23169375 · Cited by 13
“In the last decade, a multitude of clinical and laboratory studies have implicated miR-210 as the most significant modulator of the hypoxia-induced derangements in mitochondrial function [25,26], as well as the modulation of the ensuing apoptotic cell death [27–34].”
BackgroundKelly, N. J., & Chan, S. Y. (2022) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2311378 · Cited by 14
“Our group previously identified a hypoxia-inducible microRNA, microRNA-210 (miR-210), which translationally represses the Fe-S cluster assembly enzymes ISCU1/2 and is upregulated in PAH [124,125].”
Self-citationResearch progress on miR-124-3p in the field of kidney disease
Chen, G., Wang, Y., Zhang, L., Yang, K., Wang, X., & Chen, X. (2024) · BMC Nephrology · doi:10.1186/s12882-024-03688-7 · Cited by 13
“Additionally, miRNAs regulate nuclear-encoded mitochondrial proteins [66] and mitochondrial metabolism [67, 68].”
BackgroundAlibrandi, L., & Lionetti, V. (2025) · Vascular Pharmacology · doi:10.1016/j.vph.2025.107476 · Cited by 14
Aalaei‐Andabili, S. H., Fabbri, M., & Rezaei, N. (2013) · Immunotherapy · doi:10.2217/imt.13.112 · Cited by 13
Chen, Y., Zheng, J., & Chen, J. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200617163857 · Cited by 13
The role of redox system in metastasis formation
Cencioni, C., Comunanza, V., Middonti, E., Vallariello, E., & Bussolino, F. (2021) · Angiogenesis · doi:10.1007/s10456-021-09779-5 · Cited by 13
Leslie, E., Lopez, V., Anti, N. A. O., Alvarez, R., Kafeero, I., Welsh, D. G., Romero, M., Kaushal, S., Johnson, C., Bosviel, R., et al. (2021) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00469.2020 · Cited by 13
Transcription-Based Multidimensional Regulation of Fatty Acid Metabolism by HIF1α in Renal Tubules
Li, W., Duan, A., Xing, Y., Xu, L., & Yang, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.690079 · Cited by 13
“…Silva Rosa et al., 2020), HMOX1 (Zukor et al., 2009; Meyer et al., 2018), PDK4 (Oh et al., 2017; Ma et al., 2020), Frontiers in Cell and Developmental Biology | www.frontiersin.org 6 July 2021 | Volume 9 | Article 690079 and MIR210 (microRNA-210) (Chan et al., 2009; Nakada et al., 2020; Table 1).”
BackgroundInfluentialKaitsuka, T., Matsushita, M., & Matsushita, N. (2021) · Cells · doi:10.3390/cells10123316 · Cited by 14
“reported that miR-210 targets iron-sulfur cluster assembly protein (ISCU1/2) and represses mitochondrial respiration and associated downstream processes in hypoxic conditions [38].”
BackgroundNon-coding RNAs: New players in mitophagy and neurodegeneration
Tai, Y., Chen, J., Tao, Z., & Ren, J. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105253 · Cited by 13
Mammalian mitochondrial iron–sulfur cluster biogenesis and transfer and related human diseases
Wenxin, Z., Xu, L., Hongting, Z., & Li, K. (2021) · Biophysics Reports · doi:10.52601/bpr.2021.200038 · Cited by 12
“miR210 can effectively inhibit ISCU translation by binding to the 3'-UTR of ISCU mRNA (Chan et al. 2009).”
Yak miR‐2285o‐3p attenuates hypoxia‐induced apoptosis by targeting caspase‐3
Zhang, J., Long, K., Wang, J., Zhang, J., Jin, L. G., Tang, Q., Li, X., Ma, J., Li, M., & Jiang, A. (2021) · Animal Genetics · doi:10.1111/age.13153 · Cited by 14
“…Bcl-2 during lung development in chickens (Hao et al. 2014), and hypoxia-induced miR-210 controls metabolic adaptation under hypoxia by targeting the iron– sulfur cluster assembly proteins ISCU1/2 in arterial (Chan et al. 2009) and pulmonary vascular endothelium cells (Chan et al. 2009).”
BackgroundInfluentialHu, X., Song, R., Dasgupta, C., Blood, A. B., & Zhang, L. (2023) · The Journal of Physiology · doi:10.1113/jp284336 · Cited by 13
“…been shown to have a common effect and suppress mitochondrial respiration in the placenta and/or trophoblast (Colleoni et al., 2013;Muralimanoharan et al., 2012). miR-210-induced mitochondrial dysfunction is associated with increased mtROS (Chan et al., 2009; Favaro et al., 2010; Ma et al., 2019).”
BackgroundCaron, J. M., & Caron, J. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0141565 · Cited by 12
“This repression causes a disruption of iron-sulfur cluster (Fe-S cluster) biogenesis in the mitochondria [28].”
BackgroundEffects of treatment with androgen receptor ligands on microRNA expression of prostate cancer cells
Segal, C. V., Koufaris, C., Powell, C. J., & Gooderham, N. J. (2015) · Toxicology · doi:10.1016/j.tox.2015.04.002 · Cited by 12
Improving stem cell therapy in cardiovascular diseases: the potential role of microRNA
Nollet, E., Hoymans, V. Y., Craenenbroeck, A. H. V., Vrints, C. J., & Craenenbroeck, E. M. V. (2016) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00239.2016 · Cited by 12
Yao, Q., Parvez-Khan, M., & Schipani, E. (2020) · Bone · doi:10.1016/j.bone.2020.115572 · Cited by 12
Scopetti, M., Padovano, M., Manetti, F., Fazio, N. D., Radaelli, D., D’Errico, S., Frati, P., & Fineschi, V. (2023) · International Journal of Medical Sciences · doi:10.7150/ijms.79539 · Cited by 11
“Nonetheless, the comparison between the expression profiles of hypoxamiRs and immunohistochemical markers of hypoxic stress on lung tissue could contribute to increasing the sensitivity and specificity in diagnosing the vitality of exposure to hypoxic insult [28-30].”
BackgroundRole of MicroRNAs in Regulation of Cellular Response to Hypoxia
Silina, M. V., Dzhalilova, D. S., & Makarova, O. V. (2023) · Biochemistry (Moscow) · doi:10.1134/s0006297923060032 · Cited by 13
Non-coding RNAs and angiogenesis in cardiovascular diseases: a comprehensive review
Zhang, J. (2024) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-023-04919-5 · Cited by 12
“MiR-210, in particular, has the ability to suppress mitochondrial metabolism by encouraging the switch from mitochondrial respiration to glycolysis [86], preventing apoptosis [10, 15, 87, 88] along with boosting stem cell survival [89, 90].”
Hypoxia Boosts Aerobic Glycolysis in Carcinoma: A Complex Process for Tumour Development
Zheng, X., Fan, H. J., Liu, Y., Wei, Z., Li, X., Wang, A., Chen, W., & Lu, Y. (2021) · Current Molecular Pharmacology · doi:10.2174/1874467214666210811145752 · Cited by 11
Tang, H., Ayon, R. J., & Yuan, J. X. ‐. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201505160 · Cited by 11
“In agreement with their previous report, the authors confirm that Fe-S integrity in pulmonary arterial endothelial cells is directly mediated by the miR210/ISCU1/2 axis and the decrease in Fe-S levels is due to activation of miR-210 (Chan et al , 2009).”
MicroRNA-210 Regulates Dendritic Morphology and Behavioural Flexibility in Mice
Watts, M. E., Williams, G., Lü, J., Nithianantharajah, J., & Claudianos, C. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02197-6 · Cited by 11
“miR-210 dysregulation has been repeatedly associated with metabolic regulation in various cell types as well as in cortical rat neurons in vitro following oxygen-glucose deprivation [10, 20, 44].”
BackgroundHo-Xuan, H., Lehmann, G. J., Glažar, P., Gypas, F., Eichner, N., Heizler, K., Schlitt, H. J., Zavolan, M., Rajewsky, N., Meister, G., et al. (2020) · Cancers · doi:10.3390/cancers13010049 · Cited by 13
“MiR-210 is a hypoxia-induced miRNA [77,78] and associated with radio-resistance in lung cancer [79].”
BackgroundMicroRNAs in hypoxia and acidic tumor microenvironment
Jin, H., Wang, N., Wang, C., & Qin, W. (2014) · Chinese Science Bulletin · doi:10.1007/s11434-014-0273-y · Cited by 11
Harnessing the value of fertility biomarkers in bull sperm for buck sperm
Bodu, M., Hitit, M., & Memili, E. (2024) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2024.107643 · Cited by 10
Functional Repercussions of Hypoxia-Inducible Factor-2α in Idiopathic Pulmonary Fibrosis
Torres-Soria, A. K., Romero, Y., Balderas-Martínez, Y. I., Velázquez‐Cruz, R., Espíndola, L. M. T., Camarena, Á., Flores‐Soto, E., Solís‐Chagoyán, H., Ruiz, V., Carlos‐Reyes, Á., et al. (2022) · Cells · doi:10.3390/cells11192938 · Cited by 11
“It also has significant activity in microRNAs, such as miR210, which is upregulated in a HIF-1α-dependent manner, and has an inhibitory effect on cell cycle progression in Human Pulmonary Artery Endothelial Cells (Table 1) [81].”
BackgroundThe Crosstalk between Micro RNA and Iron Homeostasis
Li, Z. S. Y. (2013) · International Journal of Genomic Medicine · doi:10.4172/2332-0672.1000112 · Cited by 10
“Through modulation of ISCU, miR210 has been shown to alter mitochondrial respiratory complex activity and mitochondrial function [101-103].”
BackgroundInfluential
Metadata
- Authors
- Chan, S. Y., Zhang, Y.-Y., Hemann, C., Mahoney, C. E., Zweier, J. L., & Loscalzo, J.
- Affiliations
- Harvard University (US)
- The Ohio State University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Loscalzo, Joseph
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 10
- Issue
- 4
- Pages
- 273-284
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2759401
- OpenAlex
- W2087408461
- Cited by
- 702
- References
- 37
- Citations by year
- 2026: 33 · 2025: 44 · 2024: 30 · 2023: 24 · 2022: 45 · 2021: 73 · 2020: 44 · 2019: 50 · 2018: 29 · 2017: 51 · 2016: 35 · 2015: 38 · 2014: 59 · 2013: 60 · 2012: 39
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01hv28178-12-0-0)
- U.S. Public Health Service (P01 81587)
- National Heart, Lung, and Blood Institute (HL61795, K08HL096834, U54HL070819, P01HL081587, N01-HV-028178, R21HL089734, R01HL061795, R37HL061795)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Metalloenzymes and iron-sulfur proteins
- Keywords
- miR-210, iron-sulfur cluster assembly, hypoxia, mitochondrial metabolism, mitochondrial respiration, pulmonary artery endothelial cells, complex I, aconitase, iron-sulfur proteins
- MeSH terms
- Animals, Hypoxia, Cells, Cultured, Gene Expression Regulation, Humans, Iron-Sulfur Proteins, Mitochondria, Oxygen Consumption, Mice, Knockout, MicroRNAs, Endothelial Cells, Mice, Von Hippel-Lindau Tumor Suppressor Protein, Caspase 3, Caspase 7
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