Abstract
Benign bladder pathology resulting from prostatic hypertrophy or other causes is a significant problem associated with ageing in humans. This condition is characterized by increased bladder mass, decreased urinary flow rate, decreased compliance, and these and other changes in bladder function often subject patients to increased risk of urinary tract infection. While the physiologic attributes of benign bladder pathology have been extensively described in humans and in various animal model systems, the biochemical and molecular genetic bases for that pathology have only recently been investigated in detail. Studies demonstrate that mitochondrial energy production and utilization are severely impaired in bladder smooth muscle during benign bladder disease, and to a large extent this realization has provided a rational basis for understanding the characteristic alterations in urinary flow and compliance in bladder tissue. Recent investigations targeting the detailed molecular basis for impaired mitochondrial function in the disease have shown that performance of the organellar genetic system, and to a large extent that of relevant portions of the nuclear genetic system as well, is severely aberrant in bladder tissue. In this article, we discuss the physiologic aspects of benign bladder disease, summarize biochemical evidence for the altered mitochondrial energy metabolism that appears to underlie bladder pathology, review the structure and function of the mitochondrial genetic system, and discuss molecular genetic studies of that system which have begun to provide a mechanistic explanation for the biochemical and physiological abnormalities that characterize the disease. We also discuss areas for further research which will be critically important in increasing our understanding of the detailed causes of benign bladder pathology.
Similar content being viewed by others
References
Caine M: Neurophysiology of obstruction. In: F. Hinman (ed). Benign Prostatic Hypertrophy. Springer Verlag, New York, 1983, pp 317–428
Wein AJ, Levin RM, Barrett DM: Voiding Function: Anatomy, Physiology, and Pharmacology. In: J.W. Gillenwater, J.T. Grayhack, S.S. Howards, J.D. Duckett (eds). Adult and Pediatric Urology. Year Book Medical Publishers, Chicago, 1987
Zinner N: Urodynamic evaluation of obstruction. In: F. Hinman (ed). Benign Prostatic Hypertrophy. Springer Verlag, New York, 1983, pp 429–648
Levin RM, Monson FC, Haugaard N, Buttyan R, Hudson AP, Roelofs M, Sartore S, Wein AJ: Genetic and cellular characteristics of bladder outlet obstruction. Adv Benign Prostatic Hyperplasia 22: 263–283, 1995
Harrison SCW, Hunnam GR, Farman P, Ferguson DR, and Doyle PT: Bladder instability and denervation in patients with bladder outflow obstruction. Br J Urol 60: 519–522, 1987
Gosling JA, Gilpin SA, Dixon JS, Gilpin CJ: Decrease in the autonomic innervation of human detrusor muscle in outflow obstruction. J Urol 136: 501–504, 1986
Sterling AM, Ritter RC, Zinner N R: The physical basis of obstructive uropathy. In: F. Hinman (ed). Benign Prostatic Hypertrophy. Springer Verlag, New York, 1983, pp 433–442
Malkowicz SB, Wein AJ, Elbadawi A, Van Arsdalen K, Ruggieri MR, Levin RM: Acute biochemical and functional alterations in the partially obstructed rabbit urinary bladder. J Urol 136: 1324–1329, 1986
Santarosa R, Colombel M, Kaplan S, Monson F, Levin R, Buttyan R: Hyperpiasia and apoptosis: Opposing cellular forces that regulate the response of the rabbit bladder to transient outlet obstruction. Lab Invest 70: 503–510, 1994
Elbadawi A, Meyer S, Malkowicz SIB, Wein AJ, Levin RM, Atta A: Effects of short-term partial bladder outlet obstruction on the rabbbit detrusor, an ultrastructural study. Neurourol Urodyn 8: 89–116, 1989
Elbadawi A, Meyer S, Regnier CH: Role of ischemia in structural changes in the rabbit detrusor following partial bladder outlet obstruction: A working hypothesis and a biomechanical/structural model proposal. Neurourol Urodyn 8: 151–162, 1989
Brent L, Stephens FD: The response of smooth muscle cells in the rabbit urinary bladder to outflow obstruction. Invest Urol 12: 494–502, 1975
Kato K, Wein AJ, Kitada S, Haugaard N, Levin RM: The functional effect of mild outlet obstruction on the rabbit urinary bladder. J Urol 140: 880–884, 1988
Levin RM, Longhurst PA, Monson FC, Kato K, Wein AJ: Effect of bladder outlet obstruction on the morphology, physiology, and pharmacology of the bladder. Prostate (Suppl) 3: 926, 1990
Levin RM, Longhurst PA, Monson FC, Haugaard N, Wein AJ: Experimental studies on bladder outlet obstruction. In: H. Lepor, R.K. Lawson (eds). Prostate Diseases. WB Saunders, Philadelphia, 1993, pp 119–130
Kato K, Wein AJ, Longhurst PA, Haugaard N, Levin RM: The functional effects of long term outlet obstruction on the rabbit urinary bladder. J Urol 143: 600–606, 1990
Mattiasson A, Uvelius B: Changes in contractile properties in hypertrophic rat urinary bladder. J Urol 128: 1340–1342, 1982
Gabella G, Berggren T, Uvelius B: Hypertrophy and reversal of hypertrophy in rat pelvic ganglion neurons. J Neurocytol 21: 649–662, 1992
Steers WD, De Groat WC: Effect of bladder outlet obstruction on micturition reflex pathways in the rat. J Urol 140: 864–871, 1988
Mostwin JL, Karim OMA, Van Koeveringe G, Brooks EL: The guinea pig as a model of gradual urethral obstruction. J Urol 145: 854–858, 1991
Peters CA, Vasavada S, Dator D, Carr M, Shapiro E, Lepor H, McConnell J, Retik AB, Mandell J: The effect of obstruction on the developing bladder. J Urol 148: 491–496, 1992
Nielsen KK, Andersen CB, Petersen LK, Oxlund H, Nordling J: Morphological, stereological, and biochemical analysis of the mini-pig urinary bladder after chronic outflow obstruction and after recovery from obstruction. Neurourol Urodynam 14: 269–284, 1995
Rohner TJ, Hannigan JD, Sanford EJ: Altered in vitro adrenergic responses of dog detrusor muscle after chronic bladder outlet obstruction. Urol 11: 357–361, 1978
Cass AS, Hinman F: Constant urethral flow in female dog. I. Normal vesical and urethral pressures and effect of muscle relaxant. J Urol 99: 442–446, 1968
Kato K, Wein AJ, Radzinski C, Longhurst PA, McGuire EJ, Miller LF, Elbadawi A, Levin RM: Short term functional effects of bladder outlet obstruction in the cat. J Urol 143: 1020–1025, 1990
Radzinski C, McGuire EJ, Smith D, Wein AJ, Levin RM, Miller LF, Elbadawi A: Creation of a feline model of obstructive uropathy. J Urol 145: 859–863, 1991
Levin RM, Longhurst PA, Barasha B, MeQuire EJ, Elbadawi A, Wein AJ: Studies on experimental bladder outlet obstruction in the cat. long-term functional effects. J Urol 148: 939–943, 1992
Jorgensen TM, Djurhuud JC, Jorgensen HS, Sorensen SS: Experimental bladder hyperreflexia in pigs. Urol Res 11: 239–240, 1983
Sibley GN: An experimental model of detrusor instability in the obstructed pig. Br J Urol 57: 292–298, 1985
Speakman MJ, Brading AF, Gilpin CJ, Dixon JS, Gilpin SA, Gosling JA: Bladder outflow obstruction-a cause of denervation supersensitivity. J Urol 138: 1461–1466, 1987
Levin RM, Longhurst PA, Kato K, McGuire EJ, Elbadawi A, Wein AJ: Comparative physiology and pharmacology of the cat and rabbit urinary bladder. J Urol 143: 848–852, 1990
Longhurst PA, Kang J, Wein AJ, Levin RM: Comparative length-tension relationship of urinary bladder strips from hamsters, rats, guinea-pigs, rabbits and cats. Comp Biochem Physiol 96A: 221–225, 1990
Longhurst PA, Eika B, Leggett RE, Levin RM: Comparison of urinary bladder function in 6 and 24 month male and female rats. J Urol 148: 1615–1620, 1992
Zderic SA, Duckett JW, Wein AJ, Snyder HM, Levin RM: Developmental factors in the contractile response of the rabbit bladder to both autonomic and non-autonomic agents. Pharmacol 41: 119–123, 1990
Chun AL, Wein AJ, Harkaway R, Levin RM: Comparison of urinary bladder function in sexually mature and immature male and female rats. J Urol 143: 1267–1271, 1990
Keating MA, Levin RM: Experimental observations of bladder outlet obstruction. Dialog Ped Urol 12: 1–8, 1989
Kang J, Wein AJ, Levin RM: Bladder functional recovery following acute overdistension. Neurourol Urodyn 11: 253–261, 1992
Levin RM, Staskin DR, Wein AJ: The effects of acute overdistention of the rabbit urinary bladder. Neurourol Urodyn 2: 63–67, 1983
Monson FC, Wein AJ, Eika B, Murphy M, Levin RM: Stimulation of DNA synthesis in rabbit bladder wall after partial obstruction and acute overdistension. Neurourol Urodyn 13: 51–62, 1994
Gill HS, Monson FC, Wein AJ, Ruggieri MR, Levin RM: The Effects of short-term in vivo ischemia on the contractile function of the rabbit urinary bladder. J Urol 139: 1350–1354, 1988
Levin RM, Brendler K, Van Arsdalen KN, Wein AJ: Functional response of the rabbit urinary bladder to anoxia and ischemia. Neurourol Urodynam 2: 233–243, 1983
Lin AT, Wein AJ, Gill HS, Levin RM: Functional effect of chronic ischemia on rabbit urinary bladder. Neurourol Urodynam 7: 1–12, 1988
Cumming JA, Chisholm GD: Changes in detrusor innervation with relief of outflow tract obstruction. Br J Urol 69: 7–11, 1992
Levin RM, Malkowicz SB, Wein AJ, Atta MA, Elbadawi A: Recovery from short term obstruction of the rabbit urinary bladder. J Urol 134: 388–390, 1985
Bilgen A, Wein AJ, Zhao Y, Levin RM: The effects of anoxia on the biphasic response of isolated strips of rabbit bladder to field stimulation, bethanechol, methoxamine, and KCl. Pharmacol 44: 283–289, 1992
Levin RM, Brendler K, Wein AJ: Comparative pharmacolological response of an in vitro whole bladder preparation (rabbit) with the response of isolated smooth muscle strips. J Urol 30: 377–381, 1983
Levin RM, Ruggieri MR, Gill HS, Haugaard N, Wein AJ: Studies on the biphasic nature of urinary bladder contraction and function. Neurourol Urodynam 6: 339–350, 1987
Hypolite J, Wein AJ, Haugaard N, Levin RM: The role of substrates in the maintainence of contractility of the rabbit urinary bladder. Pharmacol 42: 202–210, 1991
Hsu TH-S, Levin RM, Wein AJ, Haugaard N: Alterations of mitochondrial oxidative metabolism in rabbit urinary bladder after partial outlet obstruction. Mol Cell Biochem 141: 21–26, 1994
Kato K, Lin AT-L, Wein AJ, Levin RM: Effect of outlet obstruction on glucose metabolism of the rabbit urinary bladder. J Urol 143: 844–847, 1990
Levin RM, Haugaard N, Wein AJ: Metabolic alterations induced by obstructive hypertrophy of the rabbit urinary bladder. In: Proceedings of the International Symposium 'smooth Muscle'. Jap J Pharmacol 58(suppl. II): 341–419, 1992
Levin RM, High J, Wein AJ: The effect of short-term obstruction on urinary bladder function in the rabbit. J Urol 132: 789–791, 1984
Lin AT-L, Chang LS, Chen M-T, Yang C-H, Shiao M-S, Chen C-J, Levin RM: Energetics of detrusor contraction: Effects of outlet obstruction. Neurourol Urodyn 11: 605–610, 1992
Levin RM, Ruggieri MR, Wein AJ: Functional effects of the purinergic innervation of the rabbit urinary bladder. J Pharmacol Exp Ther 236: 452–455, 1986
Levin RM, Haugaard N, Levin SS, Wein AJ: Creatine kinase activity in normal and hypertrophied rabbit urinary bladder tissue following partial outlet obstruction. Mol Cell Biochem 106: 143–149, 1991
Ghoniem GM, Regnier CH, Biancani P, Johnson L, Susset JG: Effect of vesical outlet obstruction on detrusor contractility and passive properties. J Urol 135: 1284–1289, 1986
Bilgen A, Wein AJ, Haugaard N, Packard D, Levin RM: Effect of outlet obstruction on pyruvate metabolism of the rabbit urinary bladder. Mol Cell Biochem 117: 159–163, 1992
Haugaard N, Potter L, Wein AJ, Levin RM: Effect of partial obstruction of the rabbit urinary bladder on malate dehydrogenase and citrate synthase activity. J Urol 147: 1391–1393, 1992
Annex BH, Kraus WE, Dohm GL, Williams RS: Mitochondrial biogenesis in striated muscles: Rapid induction of citrate synthase mRNA by nerve stimulation. Am J Physiol 260: C266–C270, 1991
Altmann B (1894). Cited in: E.D.P. de Robertis, W.W. Nowinski, F.A. Saez (eds). Cell Biology. WB Saunders, Philadelphia, 1970, pp 199–228
Benda (1897). Cited in: E.D.P. de Robertis, W.W. Nowinski, F.A. Saez (eds). Cell Biology. WB Saunders, Philadelphia, 1970, pp 199–228
Tzagoloff A: Mitochondria. Plenum Press, New York, 1982
Dujon B: Mitochondrial Genetics and Functions. In: J.N. Strathern, E.W. Jones, J.R. Broach (eds). Molecular Biology of the Yeast Saccharomyces; Life Cycle, and Inheritance. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1981, pp 505–635
Gray MW: The endosymbiont hypothesis revisited. Int Rev Cytol 141: 233–257, 1992
Jeon KW, Friedlander M: Mitochondrial Genomes. Int Rev Cytol 141: Academic Press, New York, 1992
Gray MW: Origin and evolution of mitochondrial DNA. Annu Rev Cell Biol 5: 25–50, 1989
Lang BF, Burger G, O'Kelly CJ, Cedergren R, Golding GB, Lemieux C, Sankoff D, Turmel M, Gray MW: An ancestral mitochondrial DNA resembling a eubacterial genome in miniature. Nature 387: 493–497, 1997
Anderson S, deBruijn MHL, Coulson AR, Eperon IC, Sanger F, Young IG: Complete sequence of bovine mitochondrial DNA, conserved features of the mammalian mitochondrial genome. J Mol Biol 156: 683–717, 1982
Bibb MJ, Van Etten RA, Wright CT, Walberg MW, Clayton DA: Sequence and gene organization of mouse mitochondrial DNA. Cell 26: 167–180, 1981
Borst P, Grivell: The mitochondrial genome of yeast. Cell 15: 705–723, 1978
Roe BA, Ma D-P, Wilson RK, Wong JF-H: The complete nucleotide sequence of the Xenopus laevis mitochondrial genome. J Biol Chem 260: 9759–9774, 1985
Clayton DA: Replication/transcription of vertebrate mitochondrial DNA. Annu Rev Cell Biol 7: 453–478, 1991
Shadel GS, Clayton DA: Mitochondrial DNA maintenance in vertebrates. Annu Rev Biochem 66: 409–435,1997
Terpstra P, Butow RA: The role of var1 in the assembly of mitochondrial ribosomes. J Biol Chem 254: 12662–12669, 1979
Lazowska J, Jacq C, Slonimski PP: Sequence of introns and flanking exons in the wild-type and box3 mutants of mitochondriai cytochromeb gene reveals an interiaced splicing protein coded by an intron. Cell 22: 333–348, 1980
Clayton DA: Transcription of the mammalian mitochondrial genome. Annu Rev Biochem 53: 575–594, 1984
Shadel GS, Clayton DA: Mitochondrial transcriptional initiation. J Biol Chem 268: 16083–16086, 1993
Insdorf NF, Bogenhagen DF: DNA polymerase γ from Xenopus laevis. I. Identification of a high molecular weight catalytic subunit by a novel DNA polymerase photolabelling procedure. J Biol Chem 264: 21491–21497, 1989
Longley MJ, Mosbaugh DW: Properties of the 3′ to 5′ exonuclease associated with porcine liver DNA polymerase γ. J Biol Chem 266: 24702–24711, 1991
Wernette CM, Kaguni LS: A mitochondrial DNA polymerase from embryos of Drosophila melanogaster. Purification, subunit structure, and partial characterization. J Biol Chem 261: 14764–14770, 1986
Gray H, Wong TW: Purification and identification of subunit structure of the human mitochondrial DNA polymerase. J Biol Chem 267: 5835–5841, 1992
Foury F: Cloning and sequencing of the nuclear gene MIP1 encoding the catalytic subunit of the yeast mitochondrial DNA polymerase. J Biol Chem 264: 20552–20560, 1989
Ropp PA, Copeland WC: Characterization of a new DNA polymerase from Schizosaccharomyces pombe: A probably homologue of the Saccharomyces cerevisiae DNA polymerase gamma. Gene 165: 103–107, 1995
Lewis DL, Farr CL, Wand Y, Lagina AT, Kaguni LS: Catalytic subunit of mitochondrial DNA polymerase from Drosophila embryos. J Biol Chem 271: 23389–23394, 1996
Ropp PA, Copeland WC: Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase γ. Genomics 36: 449–458, 1996
Ye F, Carrodeguas JA, Bogenhagen DF: The γ subfamily of DNA polymerases, cloning of a developmentally regulated cDNA encoding Xenopus laevis mitochondrial DNA polymerase γ. Nucl Acids Res 24: 1481–1488, 1996
Lecrenier N, Van Der Bruggen P, Foury F: Mitochondrial DNA polymerases from yeast to man: A new family of polymerases. Gene 185: 147–152, 1997
Watanabe TK, Shimizu F, Nishino N, Fujiwara T, Kanemoto N, Suzuki M, Nakamura Y, Hirai Y, Maekawa H, Takahashi E: Unpublished data submission to GenBank. Accession number D84103, 1996
Chang S-W, Colvin S, Sarkos P, Denninger G, Zassenhaus HP: Unpublished data submission to GenBank. Accession number U53584, 1996
Wang Y, Farr CL, Kaguni LS: Accessory subunit of mitochondrial DNA polymerase from Drosophila embryos. J Biol Chem 272: 13640–13646, 1997
Mignotte B, Barat M, Mounolou J-C: Characterization of a mitochondrial protein binding to single-stranded DNA. Nucl Acids Res 13: 1703–1716, 1985
Ghrir R, Lecaer J-P, Dufresne C, Gueride M: Primary structure of the two variants of Xenopus laevis mtSSB, a mitochondrial DNA binding protein. Arch Biochem Biophys 291: 395–400, 1991
Van Dyck E, Foury F, Stillman B, Brill SJ: A single-stranded DNA binding protein required for mitochondrial DNA replication in S. cerevisiae is homologous to E. coli SSIB. EMBO J 11: 3421–3430, 1992
Davis DG, Ropp PA, Clayton DA, Copeland WC: Mitochondrial DNA polymerase γ is expressed and translated in the absence of mitochondrial DNA maintenance and replication. Nucl Acids Res 24: 2753–2759, 1996
Levens D, Lustig A, Rabinowitz M: Purification of mitochondrial RNA polymerase from Saccharomyces cerevisiae. J Biol Chern 256: 1474–1481, 1981
Kelly JL, Greenleaf AL, Lehman IR: Isolation of the nuclear gene encoding a subunit of the yeast mitochondrial RNA polymerase. J Biol Chem 261: 10348–10351, 1987
Schinkel AH, Groot Koerkamp WA, Touw EP, Tabak HF: Specificity factor of yeast mitochondrial RNA polymerase. Purification and interaction with core RNA polymerase. J Biol Chem 262: 12785–12791, 1987
Tracy RL, Stem DB: Mitochondrial transcriptional initiation: Promoter structures and RNA polymerases. Curr Genet 28: 205–216, 1995
Dieckmann CL, Staples RR: Regulation of mitochondrial gene expression in Saccharomyces cerevisiae. Int Rev Cytol 152: 145–181, 1993
Costanzo MC, Fox TD: Control of mitochondrial gene expression in Saccharomyces cerevisiae. Annu Rev Genet 24: 91–113, 1990
Greenleaf AL, Kelly JL, Lehman IR: Yeast RPO41 gene product is required for transcription and maintenance of the mitochondrial genome. Proc Nati Acad Sci USA 83: 3391–3394, 1986
Masters BS, Stohl LL, Clayton DA: Yeast mitochondrial RNA polymerase is homologous to those encoded by the bacteriophages T3 and T7. Cell 51: 89–99, 1987
Lisowsky T, Michaelis G: A nuclear gene essential for mitochondrial DNA replication supresses a defect of mitochondrial transcription in Saccharomyces cerevisiae. Mol Gen Genet 214: 218–223, 1988
Lisowsky T, Michaelis G: Mutations in the genes for mitochondrial RNA polymerase and a second mitochondrial transcription factor of Saccharomyces cerevisiae. Mol Gen Genet 219: 125–128, 1989
Jang SH, Jaehning JA: The yeast mitochondrial RNA polymerase specificity factor, MTF1, is similar to bacterial factors. J Biol Chem 266: 22671–22677, 1991
Shadei GS, Clayton DA: A Saccharomyces cerevisiae transcription factor, sc-mtTFB, shares features with sigma factor but is functionally distinct. Mol Cell Biol 15: 2101–2108, 1995
Mangus DA, Jang SH, Jaehning A: Release of the yeast mitochondrial RNA polymerase specificity factor from transcription complexes. J Biol Chem 269: 26568–26574, 1994
Lisowsky T, Riemen G, Michaelis G: Change of serine309 into proline causes temperature sensitivity of the nuclear NAM1/MTF2 gene product for yeast mitochondria. Nucl Acids Res 18: 7163, 1990
Pande S, Lemire EG, Nargang FE: The mitochondrial plasmid from Neurospora intermedia strain Labelle-1b contains a long open reading frame with blocks of amino acids characteristic of reverse transcriptases and related proteins. Nucl Acids Res 17: 2023–2042,1989
Tiranti V, Savoia A, Forti F, D'Apolito M-F, Centra M, Rocchi M, Zeviani M: Identification of the gene encoding the human mitochondrial RNA polymerase (h-mtRPOL) by cyberscreening of the expressed sequence tags database. Hum Mol Genet 6: 615–625, 1997
Cermakian N, Ikeda TM, Cedergren R, Gray MW: Sequences homologous to yeast mitochondrial and bacteriophage T3 and T7 RNA polymerases are widespread throughout the eukaryotic lineage. Nucl Acids Res 24: 648–654, 1996
Hopper AK, Martin NC: Processing of yeast cytoplasmic and mitochondrial precursor tRNAs. In: JR Broach, JR Pringle, EW Jones (eds). Molecular Biology of the Yeast Saccharomyces: Gene Expression (Vol 2). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 1992, pp 216–244
Christianson T, Edwards J, Levens D, Locker J, Rabinowitz M: Transcriptional initiation and processing of the small ribosomal RNA of yeast mitochondria. J Biol Chem 257: 6494–6500, 1982
Christianson T, Edwards J, Mueller DM, Rabinowitz M: Identification of a single transcriptional initiation site for the glutamic tRNA and COB genes in yeast mitochondria. Proc Natl Acad Sci USA 80: 5564–5568, 1983
Parikh VS, Morgan MM, Scott R, Clements LS, Butow RA: The mitochondrial genome can influence nuclear gene expression in yeast. Science 235: 576–580, 1987
McEntee CM, Cantwell R, Thomas LC, Hudson AP: Mitochondrial rRNA-containing petite strains of yeast (S. cerevisiae) show a normal nuclear-mitochondrial stringent response. Biochem Biophys Res Commun 164: 362–369, 1989
McEntee CM, Cantwell R, Rahman MU, Hudson AP: Transcription of the yeast mitochondrial genome requires cAMP. Mol Gen Genet 241: 213–224, 1993
McEntee CM, Cantwell R, Hudson AP: Regulation of stringent mitochondrial transcription in yeast following amino acid deprivation. Gene 141: 129–132, 1994
Rahman MU, Keyman TR, McEntee CM, Hudson AP: Regulation of mitochondrial cAMP dependent protein kinase activity in yeast. Biochem Mol Biol Int 34: 745–753, 1994
Iqbal J, Rahman MU, Gérard HC, Yu J, Nevel CA, Hudson AP: A probable cis-regulatory element on yeast mitochondrial DNA responsible for cAMP-dependent transcription. Curr Genet 30: 493–501, 1996
Fisher RP, Clayton DA: A transcription factor required for promoter recognition by human mitochondrial RNA polymerase. J Biol Chem 260: 11330–11338, 1985
Fisher RP, Topper JN, Clayton DA: Promoter selection in human mitochondria involves binding of a transcription factor to orientation-independent upstream regulatory elements. Cell 50: 247–258, 1987
Fisher RP, Parisi MA, Clayton DA: Flexible recognition of rapidly evolving promoter sequences by mitochondrial transcription factor 1. Genes Devel 3: 2202–2216, 1989
Parisi MA, Xu B, Clayton DA: A human mitochondrial transcriptional activator can functionally replace a yeast mitochondrial HMG-box protein both in vivo and in vitro. Mol Cell Biol 13: 1951–1961, 1993
Glaichenhaus N, Leopoid P, Cuzin F: Increased levels of mitochondrial gene expression in rat fibroblast cell immortalized or transformed by viral and cellular oncogenes. EMBO J 5: 1261–1265, 1986
Black RJ, Friedman RM: Cytokines and oncogene activity. Cancer Surv 8: 725–39, 1989
Shan B, Vazquez E, Hanson RW: Interferon selectively inhibits the expression of mitochondrial genes: A novel pathway for interferon-mediated responses. EMBO J 9: 4307–4314, 1988
Mitchell PJ, Tjian R: Transcriptional regulation in mammalian cells by sequence specific DNA binding proteins. Science 245: 371–378, 1989
Renkawitz R: Transcriptional repression in eukaryotes. Trends Genet 6: 192–197, 1990
Guarente L, Mason T: Heme regulates transcription of the CYC1 gene of S. cerevisiae via an upstream activation site. Cell 32: 1279–1286, 1983
Guarente L: Regulatory proteins in yeast. Annu Rev Genet 21: 425–452, 1987
Pfeifer K, Arcangioli A, Guarente L: Yeast HAP1 activator competes with the factor RC2 for finding to the upstream activation site UAS1 of the CYC1 gene. Cell 49: 9–18, 1987
Pfeifer K, Prezant T, Guarente L: Yeast HAP1 activator binds to two upstream activation sites of different sequences. Cell 49: 19–27, 1987
Olesen J, Hahn S, Guarente L: Yeast HAP2 and HAP3 activators both bind to the CYC1 upstream activation site, UAS2, in a interdependent manner. Cell 51: 953–961, 1987
Dennis PP: Influence of the stringent control system on the transcription of ribonucleic acid and ribosomal protein genes in Escherichia coli. J Bacteriol 129: 580–588, 1977
Nomura M, Gourse R, Baughman G: Regulation of the synthesis of ribosomes and ribosomal components. Annu Rev Biochem 53: 75–117, 1984
Gross KJ, Pogo AO: Control mechanism of ribonucleic acid synthesis in eukaryotes. J Biol Chem 249: 568–576,1974
Oliver SG, McLaughlin CS: The regulation of RNA synthesis in yeast. 1. Starvation experiments. Mol Gen Genet 154: 145–153, 1977
Warner JR, Gorenstein C: Yeast has a true stringent response. Nature 275: 338–339, 1978
Ray DB, Butow RA: Regulation of mitochondrial ribosomal RNA synthesis in yeast. I. In search of a relaxation of stringency. Mol Gen Genet 20: 227–238, 1979
Ray DB, Butow RA: Regulation of mitochondrial ribosomal RNA synthesis in yeast. II. Effects of temperature sensitive mutants defective in cytoplasmic protein synthesis. Mol Gen Genet 20: 239–248
Cantwell R, McEntee CM, Hudson AP: Regulation of mitochondrial transcription during the stringent response in yeast. Curr Genet 21: 241–247, 1992
Suzuki H, Y Hosokawa, H Toda, Nishikimi M, Ozawa T: Common protein binding sites in the 5′-flanking regions of human genes for cytochrome c1 and ubiquinone-binding protein. J Biol Chem 265: 8159–8163, 1990
Dorsman JC, van Heeswijk WC, Grivell LA: Identification of two factors which bind to the upstream regulatory sequences of a number of nuclear genes coding for mitochondrial proteins and to genetic elements important for cell division in yeast. Nucl Acids Res 16: 7287–7301, 1988
Suzuki H, Hosokawa Y, Nishikimi M, Ozawa T: Existence of common homologous elements in the transcriptional regulatory regions of human nuclear genes and mitochondrial gene for the oxidative phosphorylation system. J Biol Chem 266: 2333–2338, 1991
Nagley P: Coordination of gene expression in the formaton of mammalian mitochondria. Trends Genet 7: 1–4, 1991
Byrne E, Trounce I, Dennett XZ: Mitochondrial theory of senescence: Respiratory chain protein studies in human skeletal muscle. Mech Ageing Dev 60: 295–302, 1991
Cooper JM, Mann VM, Schapira AH: Analysis of mitochondrial respiratory chain function and mitochondrial DNA depletion in human skeletal muscle: Effect of ageing. J Neurol Sci 113: 91–98, 1992
Wei YH: Mitochondrial DNA alterations as ageing associated molecular events. Mutat Res 275: 3–6, 1992
Shoffner JM, Wallace DC: Oxidative phosphorylation diseases. In: C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle (eds). The Metabolic and Molecular Bases of Inherited Diseases. McGraw Hill, New York, 1995, pp 1535–1609
Lesko SA, Lorentzen RJ, Ts'o PO: Role of superoxide in DNA strand scission. Biochemistry 19: 3023–3028, 1980
Miquel J, Fleming J: A two step hypothesis on the mechanisms of in vitro cell ageing-cell differentiation followed by intrinsic mitochondrial mutagenesis. J Expt Gerontol 19: 31–36, 1984
Miquel J, Economos AC, Fleming J, Johnson JE: Mitochondrial role in cell ageing. J Expt Gerontol 15: 575–591, 1980
Brown WM, George MJR, Wilson AC: Rapid evolution of animal mitochondrial DNA. Proc Nat Acad Sci (USA)76: 1971–1976, 1979
Bodner AG, Cooper JM, Leonard JV, Schapira AV: Respiratory-deficient human fibroblasts exhibiting defective mitochondrial DNA replication. Biochem J 305: 817–820, 1995
Ricci E, Moraes CT, Servidei S, Tonali P, Bonilla E, DiMauro S: Disorders associated with depletion of mitochondrial DNA. Brain Pathol 2: 141–147, 1992
Hess JF, Parisi MA, Bennett JL, Clayton DA: Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS mitochondrial encephalomyopathies. Nature 351: 236–239, 1991
Linnane AW, Marzuki S, Ozawa T, Tanaka M: Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet I(8639): 642–645, 1989
Ritcher C: Do mitochondrial DNA fragments promote cancer and ageing? FEBS Letts 241: 1–5, 1988
Wallace DC: Maternal genes, mitochondrial diseases. In: Birth defects (Original article series). 23: 137–190, 1987
Wallace DC: Mitochondrial DNA mutation and neuromuscular disease. Trends Genet 5: 9–13, 1989
Wallace DC: Mitochondrial genetics, a paradigm for ageing and degenerative diseases? Science 256: 628–632, 1992
Morgan-Hughes JA: Mitochondrial diseases. Trends Neurosci 9: 15–19, 1986
Newman NJ, Lott MT, Wallace DC: The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am J Ophthalmol 111: 750–762, 1991
Shoffner JM, Lott MT, Wallace DC: MERRF: A model disease for understanding the principles of mitochondrial genetics. Rev Neurol 147: 431–435, 1991
Zeviani M, Servidei S, Gellera C, Bertini E, DiMauro S: An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. Nature 339: 309–311, 1989
Holt IJ, Harding AE, Petty RK, Morgan-Hughes JA: A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet 46: 428–433, 1990
Holt IJ, Harding AE, Morgan-Hughes JA: Deletion of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331: 717–719, 1988
Calleja M, Pena P, Ugaide C, Ferreiro C, Marco M, Garesse R: Mitochondrial DNA remains intact during Drosophila ageing but the levels of mitochondrial transcripts are significantly reduced. J Biol Chem 268: 18891–18897, 1993
Gadaleta MN, Petruzzsella V, Daddobbo L, Olivieri C, Fracasso F, Polosa PL, Pantatore AD: Mitochondrial DNA transcription and translation in aged rat. Ann NY Acad Sci 717: 150–160, 1994
Trounce I, Byrne E, Marzuki S: Decline in skeletal muscle mitochondrial respiratory chain function: Possible factor in ageing. Lancet I(8639): 637–639, 1989
Muller-Hocker J: Cytochrome c oxidase deficient fibres in the limb muscle and diaphram of man without muscular disease: An age-related alteration. J Neurol Sci 100: 14–21, 1990
Buttyan R, Jacobs BZ, Blaivas JG, Levin RM: Early molecular response to rabbit bladder outlet obstruction. Neurourol Urodynam 11: 253–260, 1992
Mizzen LA, Chang C, Garrels JG, Welch WJ: Identification and purification of two mammalian stress proteins present in mitochondria: One related to hsp70 EL. J Biol Chem 270: 12312–12317, 1994
Ungerman C, Neupert W, Cyr DM: The role of hsp70 in conferring unidirectionality on protein translocation into mitochondria. Science 266: 1250–1254, 1994
Zhao Y, S Chacko, RM Levin: Expression of stress proteins (HSP-70 and HSP-90) in the rabbit urinary bladder subjected to partial outlet obstruction. Mol Cell Biochem 130: 49–55, 1994
Schneider HC, Berthold J, Bauer MF, Dietmeier K, Buiard B, Brunner M, Neupert W: Mitochondrial hsp70-MIM44 complex facilitates protein import. Nature 371: 768–771, 1994
Barbacid M: ras genes. Annu Rev Biochem 56: 779–827, 1987
Bollag G, McCormick F: Regulators and effectors of ras proteins. Annu Rev Cell Biol 7: 601–632, 1991
Broek D: Eukaryotic RAS proteins and yeast proteins with which they interact. Curr Top Microbiol Immunol 147: 155–169, 1989
Crews CM, Erikson RL: Extracellular signals and reversible protein phosphorylation: What to Mek of it all. Cell 74: 215–217, 1993
Gibbs JB, Marshall MS: The ras oncogene-an important regulatory element in lower eukaryotic organisms. Microbiol Revs 53: 171–185, 1989
Zhao Y, Levin RM, Levin SS, Nevel CA, Haugaard N, Hudson AP: Partial outlet obstruction of the rabbit bladder causes major changes in the mitochondrial genetic system. Mol Cell Biochem 141: 47–55, 1994
Nevel-McGarvey CA, Levin RM, Hudson AP: Transcription of mitochondrial and mitochondria-related nuclear genes in rabbit bladder following partial outlet obstruction. Mol Cell Biochem 173: 95–102, 1997
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
nevel-McGarvey, C.A., Levin, R.M., Levin, R.M. et al. Mitochondrial involvement in bladder function and dysfunction. Mol Cell Biochem 194, 1–15 (1999). https://doi.org/10.1023/A:1006983412952
Issue Date:
DOI: https://doi.org/10.1023/A:1006983412952