Mitochondrial and cell cycle functions of slimp

• Autores: Albert Antolín Fontes
• Directores de la Tesis: Lluís Ribas de Pouplana (dir. tes.), Antonio Zorzano Olarte (tut. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2019
• Idioma: español
• Tribunal Calificador de la Tesis: Montserrat (Corominas Guiu) Corominas (presid.), Miriam Royo Expósito (secret.), Ita Cruic Sovulj (voc.)
• Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad de Barcelona
• Materias:
  • Ciencias de la vida
    • Biología animal (zoología)
      • Citología animal
      • Fisiología animal
      • Invertebrados
    • Biología de insectos (entomología)
      • Fisiología de los insectos
• Texto completo no disponible (Saber más ...)
• Resumen

  • Mitochondrial and cell cycle functions of SLIMP The mitochondrial Seryl-tRNA Synthetase (SerRS2) is a member of the class II tRNA synthetase family. The mature enzyme catalyses the ligation of serine to tRNASer in mitochondria. During the process of constructing a model for human disorders caused by mitochondrial tRNA aminoacylation deficiencies in Drosophila melanogaster, a previously uncharacterized paralogue of SerRS2 named Seryl-tRNA synthetase-Like Insect Mitochondrial Protein (SLIMP) was identified. SLIMP is a new type of aminoacyl tRNA synthetase-like protein that has acquired an essential function in insects. This fast evolving paralogue is a mitochondrial RNA-binding protein which lacks tRNA aminoacylation activity. It has been previously demonstrated that mitochondrial SLIMP interacts with its homologue SerRS2 and also with LON protease. We confirmed these interactions and we described the function of SLIMP by depleting its protein levels in Drosophila melanogaster S2 cells, which led to severe defects in mitochondrial function and cell cycle arrest. We found that SLIMP simultaneously acts as a regulator of DNA replication and translation in the mitochondria and, as regulator of cell cycle progression. We show that SLIMP activates mitochondrial protein synthesis through its interaction with SerRS2 and regulates mitochondrial DNA levels by stimulating TFAM digestion by the protease LON. SLIMP was previously reported to be required for correct cell cycle progression. We showed that the depletion of a non-mitochondrial pool of SLIMP causes cell cycle arrest in G2 and the activation of E2F-related and G2/M check-point genes. Our results indicate that SLIMP activity provides an important protein for the communication between mitochondrial anabolism and cell cycle regulation.