IBMB SEMINAR, Monday, February 10th 14:30 PM | MIRIAM FERRANDO & SERGI VAZQUEZ MONTEAGUDO

Date: Monday, February 10th | Felix Serratosa room | 10|02|2025

Time: 14:30 PM

Speaker: Miriam Ferrando
Aragay Lab

Title: “Gα q , a master regulator of organelle contacts“

Abstract: Lysosomes and mitochondria are highly dynamic organelles essential for cellular homeostasis, and their dysfunction is implicated in numerous diseases. The contacts between these organelles are critical for proper cellular function and are finely regulated by a tethering/untethering protein machinery that includes Rab7, the RabGAP protein TBC1D15, and the mitochondrial protein Fis1. Our proteome analysis, in vitro immunoprecipitation, and pull-down studies have identified Fis1 and TBC1D15 as interacting partners of Gα q in mitochondria. Notably, in the absence of Gα q : lysosomes increase in size and exhibit enhanced contacts with mitochondria; RILP particles become dispersed, suggesting dysregulation of Rab7-mediated transport. Since RILP functions as a dynein/dynactin adaptor recruited by active Rab7 to mitophagosomes the observed increase in mitophagy suggests a key role for Gα q . The regulation of Rab7 activity by TBC1D15 is also important for the transport of cholesterol out of endolysosomes. The levels of cholesterol alter the transport of mitophagosomes. Cells depleted of Gα q exhibit reduced cholesterol levels in endolysosomes and a notable increase in lipid droplets. These findings support the role of the G protein cycle as a key regulator of mitochondria-lysosome contacts and mitophagy.

Speaker: Sergi Vázquez Monteagudo
Verdaguer Lab

Title: “Functional characterization of replicative complexes of RNA virus. The SARS-CoV-2 coronavirus.”

Abstract: SARS-CoV-2, like other RNA viruses, exhibits a high degree of variability that difficult viral disease control. Previously, 41 amino acid substitutions in nsp12, the main subunit of the RNA dependent RNA polymerase, were identified from patient samples. Eight of these and other designed mutations were characterized in vitro. Our results reveal a hydrophobic cluster on the contact interface of nsp12 with its cofactors that is critical for the modulation of the SARS-CoV-2 RdRp activity, offering an alternative target for antiviral design. Also, our research aims to provide insights of the polymerase fidelity and the use of antiviral nucleotide analogues against nsp12 variants.

Seminar Room: Fèlix Serratosa