2.11 Degradation Systems PDF

2.11 SISTEMAS DE DEGRADACIÓN Generalidades Proteosoma Peroxisoma Lisosoma  Generalidades Función Diferentes sistemas de degradación Proteasoma: Degradación de proteínas. Regula la calidad y la cantidad de proteínas en la célula...

2.11 SISTEMAS DE DEGRADACIÓN Generalidades Proteosoma Peroxisoma Lisosoma  Generalidades Función Diferentes sistemas de degradación Proteasoma: Degradación de proteínas. Regula la calidad y la cantidad de proteínas en la célula Peroxisomas: Síntesis y degradación de lípidos y compuestos tóxicos. Regula el metabolismo de lípidos y los sistemas Redox. Lisosomas: Digestión intracelular y eliminación de desechos. Previene la acumulación de material no deseado en la célula. We have seen how cells possess elaborate mechanisms to control a characteristic longevity or half‐life. Some protein molecules, such Estructura the rates at which proteins are synthesized. It is not unexpected Función as the enzymes of glycolysis or the globin molecules of an erythro- that cells would also possess mechanisms to control the length of cyte, are present for days to weeks. Other proteins that are required time that specific proteins survive once they are fully functional. for a specific, fleeting activity, such as regulatory proteins that initi- Proteasoma Although the subject of protein stability does not fall technically ate DNA replication or trigger cell division, may survive only a few under the heading of control of gene expression, it is a logical minutes. The destruction of such key regulatory proteins by pro- extension of that topic. Pioneering studies in the area of selective teasomes plays a crucial role in the progression of cellular pro- protein degradation were carried out by Avram Hershko and cesses (as illustrated in Figure 14.26). Velcade, a drug that Aaron Ciechanover in Israel-Orgánulo and Irwin Roseno andmembranoso Alexander encargado specifically de la digestion, inhibits proteasomal degradación de for has been approved Varshavsky in the United States. treatment of some forms of cancer. proteínas, son cilíndricas Degradation of cellular proteins is carried out within hollow, y The huecas. factors thatTamaño: 26s lifetime are not well control a protein’s cylindrical, protein‐degrading-Pueden estar machines called tanto en elunderstood. proteasomes citosolOne comoof the en el núcleo. determinants is the specific amino acid that are found in both the nucleus and cytosol of cells. Proteasomes that resides at the N‐terminus of a polypeptide chain. Polypeptides Estructura: cap 4 anillos polipeptídicosα (20s): α cap - 2 subunidades alfaβ β α subunit α -2 subunidades beta β (enzimas β 1 2 α α 3 β proteolíticas) β β subunits α 2 tapas (19s) α subunit α α α α α α cap β β β β β β El proteasoma β α β α 5 degrada β α β α 4 β α β α proteínas marcadas (a) (b) (c) reatment of some forms of cancer. Estructura Función The factors that control a protein’s lifetime are not well ¿A quién nderstood. One degrada el proteasoma? of the determinants is the specific amino acid hat resides at the N‐terminus of a polypeptide chain. Polypeptides -Proteínas mal plegadas, inestables, dañadas -Proteínas con función regulada (actúan solo en momentos especí icos) 1. Poliubiquitinación de proteínas (enzimas E1, E2, E3) -Reconocimiento de la proteína por la tapa α α β β β β 1 2 α α 3 f FROM RNA TO PROTEIN Estructura Función 1. Poliubiquitinación de proteínas (enzimas E1, E2, E3) (A) target protein with (B) polyubiquitin chain Requiere 2. Reconocimiento por la tapa de ATP unfoldase ring 3. Desenrollamiento de la cap central active sites proteína por la tapa (ATP asa) cylinder (protease) cap 4. La proteína se dirige al sitio activo donde es degradada Figure 6–87 Processive protein digestion by the proteasome. (A) The proteasome cap recognizes prot Figure 3–65B). Most of these proteins also contain an unfolded region, and the cap translocates these prot  388 Chapter 6: How Cells Read the Genome: From DNA to Protein Estructura Función introns exons En resumen: 5′ DNA 3′ La producción de una Inicio deOFlaTRANSCRIPTION INITIATION transcripción proteína por una célula eucariota Modi icación CAPPING, ELONGATION, del ARNm SPLICING cap Maduración CLEAVAGE, POLYADENYLATION, ANDdel ARNm TERMINATION AAAA mRNA EXPORT poly-A tail NUCLEUS CYTOSOL AAAA mRNA mRNA DEGRADATION Inicio INITIATIONde la síntesis OF PROTEIN de(TRANSLATION) SYNTHESIS proteínas (Traducción) AAAA Término de síntesis y plegamiento de proteínas COMPLETION OF PROTEIN SYNTHESIS AND PROTEIN FOLDING NH2 COOH Degradación PROTEIN DEGRADATION NH2 COOH f  This import receptor accompanies its cargo all the way into a protein translocator Estructura in the peroxisomal membrane. After cargo release insideFunción the peroxisome, Pex5 is recycled back to the cytosol. This recycling step requires modification of Pex5 with ubiquitin, which is used as a handle by an ATPase complex composed of Peroxisomas Pex1 and Pex6. The Pex1–Pex6 complex harnesses the energy of ATP hydroly- sis to release Pex5 from peroxisomes so it can pick up the next cargo molecule. -Orgánulo membranoso encargado de la degradación de ácidos grasos. Síntesis de colesterol y plasmalógenos. Remoción de compuestos tóxicos specific proteins that Peroxinas: catalyze protein import Catalizan la importación de FISSION proteínas al interior peroxisomal precursor peroxisome vesicle peroxisomal precursor daughter proteins Crecimiento GROWTH por captación BY UPTAKE de OF SPECIFIC peroxisomes proteínas especí PEROXISOMAL icasAND PROTEINS del LIPIDS FROM yCYTOSOL peroxisoma lípidos del citosol endoplasmic Retículo reticulum endoplasmático f  Estructura Función Peroxisomas Degradación del peróxidos Enzimas: Catalasa y urato oxidasa* B-oxidación Síntesis de colesterol Ácidos biliares  Estructura Función Lisosomas CULES IN LYSOSOMES 799 Orgánulos membranosos, muy variables. Encargados de la digestión celular, contienen más de 40 enzimas. out, they can do little 0.2–0.5 µm pH ~7.2 me not only contains CYTOSOL ounding membrane. -pH ácido: Bomba de H+ e highly glycosylated, pH ~5.0 -Membrana interna altamente the lumen. Transport HIDROLASAS ÁCIDAS: ACID HYDROLASES: ts of the digestion of nucleases Nucleasas glicosilada: Glucocálix lisosomal proteases Proteasas tides—to the cytosol, glycosidases Glucosidasas lipases Lipasas phosphatases es the energy of ATP Fosfatadas sulfatases Sulfatadas ning the lumen at its phospholipases Fosfolipasas o the family of V-type H+ and chloroplast ATP d in H+ gradients into ever, the vacuolar H+ H+ pump organelle. Similar or ATP ADP + P organelles, including  macrophages and neutrophils in vertebrates, is dedicated to the engulfment, or Estructura Función phagocytosis, of large particles and microorganisms to form phagosomes. In con- trast to these routes originating from the plasma membrane, autophagy is used to digest cytosol, worn-out organelles, and microbes that invade the cytosol. The Los lisosomas reciben material a degradar desde four paths to degradation in lysosomes are illustrated in Figure 13–67. múltiples sitios EXTRACELLULAR FLUID CYTOSOL 1. Endocitosis mediada o bacterium phagosome no por clatrina. Fagocitosis phagocytosis plasma 2. Macropinocitosis 3 membrane 3. Fagocitosis early endosome 1 4. Autofagia endocytosis Endocitosis Endosoma LATE Lisosoma LYSOSOME ENDOSOME 2 tardío mitochondrion 4 autophagosome autophagy Autofagia macropinocytosis Macropinocitosis  Estructura Función Autofagia: El reciclaje de componentes THE DEGRADATION celulares IN LYSOSOMES AND RECYCLING OF MACROMOLECULES No selectiva: engulfed cytosol and organelles -Niveles de nutrientes *Cantidad de autophagosome aminoácidos *Relación ATP/ADP INDUCTION acid hydrolases lysosome Nucleación NUCLEATION y Cierre CLOSURE Fusión WITH FUSION con Digestión DIGESTION AND EXTENSION extensión lisosomas LYSOSOMES proteins and macromolecules into building blocks that are used for other priori-  mark for a ubiquitin-dependent cargo receptor Estructura for autophagy. Mutat Función or Parkin cause a form of early-onset Parkinson’s disease, a degenera of the central nervous system. It is not known why the neurons tha Autofagia: El reciclaje turely in thisde componentes disease celulares are particularly reliant on mitophagy. r de Selectiva p t Rece nas en ubiquitin- o Mitocondria damaged q dependent b i uiti receptor del dañada mitochondrion Lisosoma lysosome u n a bra on autophagosome -Regulada por mem gosoma membrane fa auto ubiquitinación (enzimas E1, E2, E3) FusiónWITH FUSION del lisosoma y LYSOSOME, digestión DIGESTIONdel OFcargo CARGO autophagosome Autofagosoma ubiquitylated outer Membrana externa (A) membrane protein ubiquitinada Figure 13–72 Selective autophagyMitofagia is mediated by receptors that recruit cargo t (A) Diagram illustrating the concept of a cargo receptor (blue) in the autophagosome cargo, in this case a damaged mitochondrion. (B) An electron micrograph of an auto  Estructura Función Degradación del exterior e interior celular