Genes migrantes: su viaje de la mitocondria al núcleo

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  • Fig. 3. Cryo-EM tomogram of a crista junction in Saccharomyces cerevisiae. (A) Single slice through a tomogram of an isolated vitrified wild type mitochondrion from S. cerevisiae. (B) Magnified view of boxed area in left panel. (C) Surface rendered view of a crista junction. Scale bars 100 nm. EM tomogram with courtesy of Dr Marek Cyrklaff.
  • Fig. 4. Subcompartmentalization of the mitochondrial inner membrane. The distribution of mitochondrial proteins involved in several major processes of mitochondria has been determined by quantitative immunoelectron microscopy in S. cerevisiae [50]. Inner membrane proteins involved in mitochondrial fusion (Mgm1p) or protein translocation (Mia40p, TIM23 complex) are preferentially located in the inner boundary membrane. In contrast, proteins involved in oxidative phosphorylation (ANC, Complex III, Complex IV, F1FO-ATP synthase) and in iron/sulfur cluster biogenesis (Fe/S cluster) are enriched in the cristae membrane. This distribution is uneven, yet not exclusive nor static. Proteins dynamically redistribute between the domains depending on the physiological state of the cell. CS, Cytosol; OM, outer membrane; IMS, intermembrane space; IM, inner membrane; M, matrix space. Style adapted from the illustrations of Graham T. Johson in [203].
  • Changes in internal organization of mitochondria associated with cell death and disease: (A) Normal, isolated liver mitochondrion (Mannella et al., 2001), (B) Liver mitochondrion treated with a protein (tBID) that induces programmed cell death or apoptosis (Scorrano et al., 2002), and (C) Mitochondrion from a patient with a mitochondrial myopathy (M. Huizing, 1998, PhD Thesis, Univ. Nijmegen).
  • Evolution of the Molecular Machines for Protein Import into Mitochondria
    Fig. 2. The protein import machinery in mitochondria of the yeast S. cerevisiae. Arrows indicate the directional flow of protein substrates from their site of synthesis in the cytosol to each of the submitochondrial compartments. Subunits of the protein import machinery have been color-coded: Those with functional homologs in bacteria are in black, and the eukaryote-specific core components of the TOM and TIM machinery are in color. Shaded gray are components of the import machinery that are only found in fungi and animals, which suggests that they might be modules added to the machinery relatively recently. Stars depict the essential yeast proteins.
  • Genes migrantes: su viaje de la mitocondria al núcleo

    1. 1. Genes migrantes: su viaje de la mitocondria al núcleo
    2. 2. ATP
    3. 3. ADP+Pi ATP I III IV VII H+ H+ H+ H+
    4. 4. Normal, isolated liver mitochondrion Liver mitochondrion treated with a protein (tBID) that induces programmed cell death or apoptosis • Mitocondria de hígado normal • Mitocondria de hígado en apoptosis • Mitocondria de un paciente con enfermedad mitocondrial
    5. 5. Teoría endosimbiótica Konstantín Merezhkovski, 1905 Lynn Margulis, 1967
    6. 6. 1. Un fagotrofo fagocita a su presa. 2. Emergen individuos en la población de presas que son resistentes a ser digeridas 3. Emerge una relación simbiótica facultativa entre el fagotrofo y la presa 4. Cambio de endosimbionte facultativo a endosimbionte obligado 5. El endosimbionte obligado evoluciona y se convierte en organelo (mitocondria)
    7. 7. Nass & Nass 1963
    8. 8. Rickettsia tsutsugamushi dividiéndose en el interior de una célula peritoneal de ratón.
    9. 9. N Endosimbiosis primaria Endosimbiosis secundaria
    10. 10. Hace 2,000 millones de años…. …..una Archea y una α-proteobacteria….. Archea α-proteobacteria
    11. 11. Martin and Koonin (2006) Nature 440, 41-45
    12. 12. ATP6 RNA DNA Transcripción reversa
    13. 13. Homo 16.5 Kb Rickettsia 1,111.5 Kb Tetrahymena 47.3 Kb Acanthamoeba 41.6 Kb Plasmodium Reclinomonas 69.0 Kb Arabidopsis 366.9 Kb Chlamydomonas Schizosaccharomyces 19.4 Kb 17.7 Kb6.5 Kb
    14. 14. Que sucede cuando un gen migra?
    15. 15. N M A B C D E F
    16. 16. cob nad1 nad2 cox1 cox2 atp8 atp6 cox3 nad4L nad6 nad5 nad4
    17. 17. H+ H+ H+ H+ 7 33 0 1 3 2 5 10 10 15
    18. 18. Roger AJ, Silberman JD (2002) Mitochondria in hiding. Nature 418:827-829
    19. 19. Mitochondrion from chicken cerebellum Hydrogenosomes from the anaerobic fungus Neocallimastix patriciarum Hydrogenosomes from the cattle parasite Tritrichomonas foetus Mitosomes from the intestinal parasite Entamoeba histolytica, Mitosomes from the the microsporidian Trachipleistophora hominis Mitosomes from the diplomonad Giardia intestinalis
    20. 20. Chlamydomonas reinhardtii mtDNA cox 2 nad4 nad5 nad2 nad1 rtlcob cox1 nad6 17.7 Kb Chlamydomonas atp 6 ? cox 3 ? cox 2 ?
    21. 21. cox 2 cox 3 atp 6 Migración al núcleo?
    22. 22. cox 3 Cuando un gen migra de la mitocondria al núcleo…… ¿Qué sucede? ¿Qué hemos aprendido?
    23. 23. cox 3 Adquirió una región que codifica para una presecuencia mitocondrial…… N + +++ + - ++ - - + + + 100 – 140 residuos que forman alfa- hélices anfipáticas
    24. 24. cox 3 Adquieren promotores y señales de poliadenilación…… TGTAA
    25. 25. Y finalmente, sus productos proteicos muestran una hidrofobicidad disminuída… cox 3
    26. 26. COX IIB COX III ATP6 Regresando a casa….. COX IIA
    27. 27. Nada humano me es ajeno. Tertuliano
    28. 28. cob nad1 nad2 cox1 cox2 atp8 atp6 cox3 nad4L nad6 nad5 nad4
    29. 29. Paciente con mutación puntual de origen paterno en el gen nad2
    30. 30. Greg Lemond
    31. 31. Edad (años) DNAmitocondrialconablación
    32. 32. Fos-Ox X
    33. 33. Fos-Ox X+ + + A B Núcleo Atp6 Cox3 Cox2
    34. 34. Fos-Ox Fos-Ox X+ + + X A B C Núcleo
    35. 35. Células HeLa Bromuro de etidio Cíbridos (células híbridas) Fibroblastos (paciente) enucleación fusión
    36. 36. Células HeLa Bromuro de etidio Cíbridos (células híbridas) Fibroblastos primate enucleación fusión
    37. 37. H+ H+ H+ H+
    38. 38. ADP+Pi ATP I III IV VII H+ H+ H+ H+
    39. 39. N 2 x 10 -5 moléculas de DNA por célula por generación 100,000 veces menos frecuente Thorsness y Fox (1990) Nature 346: 376.
    40. 40. Claros et al. (1995) Eur. J. Biochem. 228:762 cob levadura
    41. 41. exon x exon y mt exon x exon y
    42. 42. exon x exon y mt Arabidopsis thaliana 620 kb
    43. 43. hsp70 hsp70 sdh3 hsp70 sdh3 MTS MTS MTS MTS Adams et al.(2001) Genetics 158: 1289
    44. 44. Woodward SR, Weyand NJ, Bunnell M. DNA sequence from Cretaceous period bone fragments. Science. 1994 Nov 18;266(5188):1229-32.
    45. 45. bacteria arquea Euckarya

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