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UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation

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Abstract

Mitochondria are the bioenergetic and metabolic centers in eukaryotic cells and play a central role in apoptosis. Mitochondrial distribution is controlled by the microtubular cytoskeleton. The perinuclear aggregation of mitochondria is one of the characteristics associated with some types of cell death. Control of mitochondrial aggregation particularly related to cell death events is poorly understood. Previously, we identified ubiquitously expressed transcript (UXT) as a potential component of mitochondrial associated LRPPRC, a multidomain organizer that potentially integrates mitochondria and the microtubular cytoskeleton with chromosome remodeling. Here we show that when overexpressed in mammalian cells, green fluorescent protein-tagged UXT (GFP-UXT) exhibits four types of distribution patterns that are proportional to the protein level, and increase with time. UXT initially was dispersed in the extranuclear cytosol, then appeared in punctate cytosolic dots, then an intense perinuclear aggregation that eventually invaded and disrupted the nucleus. The punctate cytosolic aggregates of GFP-UXT coincided with aggregates of mitochondria and LRPPRC. We conclude that increasing concentrations of UXT contributes to progressive aggregation of mitochondria and cell death potentially through association of UXT with LRPPRC.

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References

  • Carre, M.; Andre, N.; Carles, G., et al. Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel. J. Biol. Chem. 277:33664–33669; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Chang, K. T.; Min, K. T. Drosophila melanogaster homolog of Down syndrome critical region 1 is critical for mitochondrial function. Nat. Neurosci. 8:1577–1585; 2005.

    Article  PubMed  CAS  Google Scholar 

  • De Vos, K.; Goossens, V.; Boone, E., et al. The 55-kDa tumor necrosis factor receptor induces clustering of mitochondria through its membrane-proximal region. J. Biol. Chem. 273:9673–9680; 1998.

    Article  PubMed  Google Scholar 

  • Desagher, S.; Martinou, J. C. Mitochondria as the central control point of apoptosis. Trends Cell Biol. 10:369–377; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Ebneth, A.; Godemann, R.; Stamer, K., et al. Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer’s disease. J. Cell Biol. 143:777–794; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Frank, S.; Gaume, B.; Bergmann-Leitner, E. S., et al. The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev. Cell 1:515–525; 2001.

    Article  PubMed  CAS  Google Scholar 

  • Heggeness, M. H.; Simon, M.; Singer, S. J. Association of mitochondria with microtubules in cultured cells. Proc. Natl. Acad. Sci. U S A 75:3863–3866; 1978.

    Article  PubMed  CAS  Google Scholar 

  • Hirokawa, N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279:519–526; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Karbowski, M.; Spodnik, J. H.; Teranishi, M., et al. Opposite effects of microtubule-stabilizing and microtubule-destabilizing drugs on biogenesis of mitochondria in mammalian cells. J. Cell Sci. 114:281–291; 2001.

    PubMed  CAS  Google Scholar 

  • Kroemer, G.; Dallaporta, B.; Resche-Rigon, M. The mitochondrial death/life regulator in apoptosis and necrosis. Annu. Rev. Physiol. 60:619–642; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Li, H.; Zhu, H.; Xu, C. J.; Yuan, J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 94:491–501; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Liu, L.; McKeehan, W. L. Sequence analysis of LRPPRC and its SEC1 domain interaction partners suggest roles in cytoskeletal organization, vesicular trafficking, nucleocytosolic shuttling and chromosome activity. Genomics 79:124–136; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Liu, L.; Vo, A.; Liu, G.; McKeehan, W. L. Novel complex integrating mitochondria and the microtubular cytoskeleton with chromosome remodeling and tumor suppressor RASSF1 deduced by in silico homology analysis, interaction cloning in yeast, and colocalization in cultured cells. In Vitro Cell. Dev. Biol. Anim. 38:582–594; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Liu, L.; Vo, A.; Liu, G.; McKeehan, W. L. Distinct structural domains within C19ORF5 support association with stabilized microtubules and mitochondrial aggregation and genome destruction. Cancer Res. 65:4191–4201; 2005a.

    Article  PubMed  CAS  Google Scholar 

  • Liu, L.; Vo, A.; McKeehan, W. L. Specificity of the methylation-suppressed A isoform of candidate tumor suppressor RASSF1 for microtubule hyperstabilization is determined by cell death inducer C19ORF5. Cancer Res. 65:1830–1838; 2005b.

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Fanarraga, M.; Avila, J.; Guasch, A., et al. Review: postchaperonin tubulin folding cofactors and their role in microtubule dynamics. J. Struct. Biol. 135:219–229; 2001.

    Article  PubMed  CAS  Google Scholar 

  • Markus, S. M.; Taneja, S. S.; Logan, S. K., et al. Identification and characterization of ART-27, a novel coactivator for the androgen receptor N terminus. Mol. Biol. Cell 13:670–682; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Mili, S.; Pinol-Roma, S. LRP130, a pentatricopeptide motif protein with a noncanonical RNA-binding domain, is bound in vivo to mitochondrial and nuclear RNAs. Mol. Cell Biol. 23:4972–4982; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Mootha, V. K.; Lepage, P.; Miller, K., et al. Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics. Proc. Natl. Acad. Sci. U S A 100:605–610; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Nangaku, M.; Sato-Yoshitake, R.; Okada, Y., et al. KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria. Cell 79:1209–1220; 1994.

    Article  PubMed  CAS  Google Scholar 

  • Pendergrass, W.; Wolf, N.; Poot, M. Efficacy of MitoTracker Green and CMXrosamine to measure changes in mitochondrial membrane potentials in living cells and tissues. Cytometry A 61:162–169; 2004.

    Article  PubMed  CAS  Google Scholar 

  • Puthalakath, H.; Huang, D. C.; O’Reilly, L. A., et al. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol. Cell 3:287–296; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Sato, S.; Tatebayashi, Y.; Akagi, T., et al. Aberrant tau phosphorylation by glycogen synthase kinase-3beta and JNK3 induces oligomeric tau fibrils in COS-7 cells. J. Biol. Chem. 277:42060–42065; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Schroer, A.; Schneider, S.; Ropers, H.; Nothwang, H. Cloning and characterization of UXT, a novel gene in human Xp11, which is widely and abundantly expressed in tumor tissue. Genomics 56:340–343; 1999

    Article  PubMed  CAS  Google Scholar 

  • Silveira, H. C.; Sommer, C. A.; Soares-Costa, A.; Henrique-Silva, F. A calcineurin inhibitory protein overexpressed in Down’s syndrome interacts with the product of a ubiquitously expressed transcript. Braz. J. Med. Biol. Res. 37:785–789; 2004.

    Article  PubMed  CAS  Google Scholar 

  • Suen, Y. K.; Fung, K. P.; Choy, Y. M., et al. Concanavalin A induced apoptosis in murine macrophage PU5-1.8 cells through clustering of mitochondria and release of cytochrome c. Apoptosis 5:369–377; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Takada, S.; Shirakata, Y.; Kaneniwa, N.; Koike, K. Association of hepatitis B virus X protein with mitochondria causes mitochondrial aggregation at the nuclear periphery, leading to cell death. Oncogene 18:6965–6973; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka, Y.; Kanai, Y.; Okada, Y., et al. Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria. Cell 93:1147–1158; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Taneja, S. S.; Ha, S.; Swenson, N. K., et al. ART-27, an androgen receptor coactivator regulated in prostate development and cancer. J. Biol. Chem. 279:13944–13952; 2004.

    Article  PubMed  CAS  Google Scholar 

  • Thiselton, D. L.; McDowall, J.; Brandau, O., et al. An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders. Genomics 79:560–572; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, W. D.; Zhang, X. D. Franco, A. V., et al. TNF-related apoptosis-inducing ligand-induced apoptosis of melanoma is associated with changes in mitochondrial membrane potential and perinuclear clustering of mitochondria. J. Immunol. 165:5612–5620; 2000.

    PubMed  CAS  Google Scholar 

  • Trinczek, B.; Ebneth, A.; Mandelkow, E. M.; Mandelkow, E. Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles. J. Cell Sci. 112 (Pt 14):2355–2367; 1999.

    PubMed  CAS  Google Scholar 

  • Wolter, K. G.; Hsu, Y. T.; Smith, C. L., et al. Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol. 139:1281–1292; 1997.

    Article  PubMed  CAS  Google Scholar 

  • Zhao, H.; Wang, Q.; Zhang, H., et al. UXT is a novel centrosomal protein essential for cell viability. Mol. Biol. Cell 16:5857–5865; 2005.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This work was supported by Public Health Service Grants DK35310 from NIDDK, CA59971 and Minority Supplement Grant 3 R01 CA59971-14S from NCI, National Institutes of Health. We thank Dr. Qiang Wang, University of Pennsylvania, and Dr. Serafín Piñol-Roma of Mount Sinai School of Medicine (New York, New York) for mouse monoclonal antibody against UXT and LRPPRC, respectively, and Dr. Jian Kuang, Dept. of Cellular Oncology, MD Anderson Cancer Center for helpful advice.

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Correspondence to Leyuan Liu.

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Editor: J. Denry Sato

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Moss, T.N., Vo, A., McKeehan, W.L. et al. UXT (Ubiquitously Expressed Transcript) causes mitochondrial aggregation. In Vitro Cell.Dev.Biol.-Animal 43, 139–146 (2007). https://doi.org/10.1007/s11626-007-9016-6

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  • DOI: https://doi.org/10.1007/s11626-007-9016-6

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