Understanding the regulation of macroautophagy in health and disease: what have we learnt, so far

Il 21/09/2018 ore 14.30 - 15.30

Sala Conferenze CNR, Via P. Castellino, 111 - 80131 Napoli

Prof. Maurizio Renna from the Dipartimento di medicina molecolare e biotecnologie mediche, Università degli studi di Napoli “Federico II”, will give a seminar on the regulation of autophagy. Autophagy is a major cellular catabolic process responsible for the removal of long-lived cytoplasmic proteins, protein complexes, as well as of entire intracellular organelles, which is fundamental for the homeostasis of eukaryotic cells. Indeed, alterations of the autophagic pathways have been implicated in a large set of human diseases. Over the years, one of the major goal of the research in the field has been to identify novel pathways and molecular mechanisms regulating autophagy with the aim of providing potential alternative approaches for the treatment of many clinically relevant conditions, such as ageing, metabolic, neurodegenerative disorders, infectious diseases and cancer.

For instance, recent data report how autophagy is compromised upon contact inhibition, a phenomenon that enables normal cells to control proliferation and growth but is lost upon malignant transformation. In particular, in 2D or 3D-soft extracellular matrix cultures of contact-inhibited cells, YAP/TAZ fail to co-transcriptionally regulate the expression of myosin-II genes, resulting in the loss of F-actin stress fibers, which in turn impairs autophagosome formation. The decreased proliferation, as well as the increased sensitivity to hypoxia and glucose starvation, resulting from contact inhibition are partly autophagy-dependent. These findings define how mechanical cues mediated via the YAP/TAZ-axis impact on autophagy to contribute to core phenotypes resulting from high cell confluency, which are lost in various cancers.

Finally, preliminary data will be presented linking the activity and homeostasis of the autophagic/lysosomal compartment to the function of TDP-43, a RNA-binding protein whose mutations have been associated to some neurodegenerative diseases, such as FTD and ALS.

 

Organizzato da:
Cnr-Ibp

Referente organizzativo:
Daniela Corda
CNR - Istituto di biochimica delle proteine
Via P. Castellino, 111 - 80131 Napoli
d.corda@ibp.cnr.it
081/6132536

Modalità di accesso: ingresso libero