UAM_Biblioteca | Unified search engine | Scientific Production Portal | UAM Research Data Repository
Universidad Autónoma de Madrid
Biblos-e Archivo
We are onFacebookCanal BiblosYouTubeTwitterPinterestWhatsappInstagram
    • español
    • English
  • English 
    • español
    • English
  • Log in
JavaScript is disabled for your browser. Some features of this site may not work without it.

Search Biblos-e Archivo

Advanced Search

Browse

All of Biblos-e ArchivoCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsFacultiesThis CollectionBy Issue DateAuthorsTitlesSubjectsFaculties

My Account

Log inRegister

Statistics

View Usage Statistics

Help

Information about Biblos-e ArchivoI want to submit my workI want to submit my doctoral thesisFrequently Asked QuestionsCopyrightsFinancial Agencies and OA policy

UAM_Biblioteca

View Item 
  •   Biblos-e Archivo
  • Trabajos de estudiantes (tesis doctorales, TFMs, TFGs, etc.)
  • Trabajos de estudiantes (tesis doctorales, TFMs, TFGs, etc.)
  • View Item
  •   Biblos-e Archivo
  • Trabajos de estudiantes (tesis doctorales, TFMs, TFGs, etc.)
  • Trabajos de estudiantes (tesis doctorales, TFMs, TFGs, etc.)
  • View Item

Mitochondrial control of gene expression and extrinsic apoptosis

Author
Díaz Colunga, Juanuntranslated
Advisor
Iborra, Francisco J.; Guantes, Raúl
Entity
UAM. Departamento de Física de la Materia Condensada; CSIC. Centro Nacional de Biotecnología (CNB)
Date
2019-04-23
Subjects
Biofísica - Tesis doctorales; Citología - Tesis doctorales; Biomatemáticas - Tesis doctorales; Física
URI
http://hdl.handle.net/10486/688169
Note
Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Física de la Materia Condensada. Fecha de lectura: 23-04-2019

Licencia de Creative Commons
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.

Abstract

Even under homogeneous environmental conditions, cells with identical genotypes can display significant variations at the phenotypic level, that is, di erences in size, morphology and internal state. This is a result of the genetic and signaling circuits that control cellular functions being subject to fluctuations in the levels of their components. Cell-to-cell variability is regarded as an essential agent in many key cellular activities such as development, di erentiation, evolution, virus infection or cell death, and has been shown to serve a biological function in many cases. Thus, tracing back its sources is central to understand the behaviors of individual cells and ultimately act on them. In this work we use a combination of experimental, mathematical and computational tools to investigate the role of mitochondria (the main energy provider in eukaryotic cells) on the generation of gene expression noise. Gene expression is highly energy demanding and in turn determines phenotype, pointed as the cause of variable individual cellular responses in several processes, notably apoptosis. Heterogeneity in apoptotic outcomes is particularly relevant as it poses the main cause of tumor resistance to chemotherapy. Our results highlight the importance of mitochondria as a global modulator of gene expression, but also reveal its role regulating complex, non-linear processes like alternative splicing. We found that this control of gene expression is specially important in the apoptotic signaling pathway: mitochondria exhibit the power to discriminate apoptotic fates at the single cell level, making it a good candidate for a biomarker of the susceptibility of cancer cells to death-inducing treatments. i
 
Incluso en condiciones ambientales homog´eneas, c´elulas con genotipos id´enticos pueden presentar variaciones significativas a nivel fenot´ıpico, es decir, diferencias en tama˜no, morfolog´ıa y estado interno. Esto es el resultado de los circutos gen´eticos y de se˜nalizaci´on que controlan la funci´on celular estando sometidos a fluctuaciones en los niveles de sus componentes. La variabilidad de c´elula a c´elula es considerada un agente esencial en multitud de actividades celulares como el desarrollo, diferenciaci´on, evoluci´on, infecci´on v´ırica o la muerte celular. Por tanto, identificar sus fuentes es central para entender los comportamientos de c´elulas individuales y en ´ultima instancia actuar sobre ellos. En este trabajo utilizamos una combinaci´on de herramientas experimentales, matem´aticas y computacionales para investigar el papel de la mitocondria (principal proveedor de energ´ıa en c´elulas eucariotas) en la generaci´on de ruido en expresi´on gen´etica. La expresi´on gen´etica es costosa energ´eticamente y determina el fenotipo, se˜nalado en muchos procesos como causa de la variabilidad en las respuestas de c´elulas individuales, en particular en el de apoptosis. La heterogeneidad en los resultados apopt´oticos es particularmente relevante porque supone la principal causa de resistencia de tumores a quimioterapia. Nuestros resultados resaltan la importancia de la mitocondria como modulador global de la expresi´on g´enica, pero tambi´en revelan su papel regulando procesos complejos y no lineales como el splicing alternativo. Encontramos que este control de la expresi´on g´enica es especialmente importante en la ruta de se˜nalizaci´on apopt´otica: la mitocondria muestra el potencial de discriminar destinos apopt´oticos a nivel de c´elula ´unica, convirti´endola en un buen candidato a biomarcador de la susceptibilidad de c´elulas cancer´ıgenas frente a tratamientos inductores de apoptosis.
 
Show full item record

Files in this item

Thumbnail
Name
diaz_colunga_juan.pdf
Size
8.990Mb
Format
PDF
Description
Texto de la Tesis Doctoral

Refworks Export

Delicious Save this on Delicious

Google™ Scholar:Díaz Colunga, Juan

This item appears in the following Collection(s)

  • Trabajos de estudiantes (tesis doctorales, TFMs, TFGs, etc.) [18989]

Related items

Showing items related by title, author, creator and subject.

  • Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression 

    Márquez-Jurado, Silvia; Díaz-Colunga, Juan; Neves, Ricardo Pires das; Martinez-Lorente, Antonio; Almazán, Fernando; Guantes, Raúl; Iborra, Francisco J.
    2018-12-01
  • Modeling pathogenic mutations of human Twinkle in Drosophila melanogaster suggests that apoptosis plays a critical role in mitochondrial intergenomic communication defects 

    Sánchez Martínez, Álvaro; Calleja, Manuel; Peralta, Susana; Matsushima, Yuichi; Hernández Sierra, Rosana; Whitworth, Alexander J.; Kaguni, Laurie S.; Garesse, Rafael
    2012
  • SCaMC-1 like a member of the mitochondrial carrier (MC) family preferentially expressed in testis and localized in mitochondria and chromatoid body 

    Amigo, Ignacio; Traba, Javier; Satrústegui, Jorgina; Arco, Araceli del
    2012
All the documents from Biblos-e Archivo are protected by copyrights. Some rights reserved.
Universidad Autónoma de Madrid. Biblioteca
Contact Us | Send Feedback
We are onFacebookCanal BiblosYouTubeTwitterPinterestWhatsappInstagram
 

 

All the documents from Biblos-e Archivo are protected by copyrights. Some rights reserved.
Universidad Autónoma de Madrid. Biblioteca
Contact Us | Send Feedback
We are onFacebookCanal BiblosYouTubeTwitterPinterestWhatsappInstagram