BIFI TALK: SALVATORE ADINOLFI. Department of Drug Science and Technology, University of Turin, Italy

Título: The contradictory role of frataxin in Fe-S cluster biogenesis

Abstract:

Frataxin is a small mitochondrial protein whose limited expression impairs Fe-S cluster biogenesis and promotes iron accumulation, leading to the neurodegenerative Friedreich’s ataxia. Although frataxin role is yet to be completely unraveled, its involvement as a regulator of the desulfurase activity in the Fe-S cluster biogenesis machinery has been demonstrated for both human frataxin and its bacterial ortholog CyaY. In this frame, although the human and the bacterial proteins share high homology in their aminoacidic sequence and tridimensional structure, a dramatic discrepancy has been highlighted by in vitro studies addressing their effect on the Fe-S cluster formation machinery. In particular, while CyaY slows down the kinetics of Fe-S cluster formation on IscU, human frataxin has emerged as an activator of Fe-S cluster biogenesis. In this review it will be described all the information to better understand the evolutionary divergence of the frataxin genes.

It is difficult to clarify this apparent paradox by studying the process in vitro where the isolated proteins are in an artificial environment or in vivo under non-controlled conditions. To clarify the issue, we have used a new approach based on metabolomics to study the enzymatic reaction. We followed the enzymatic kinetics ex vivo using bacterial to investigate enzymatic kinetics of IscS and the role that frataxin plays in it. We prove that IscS is inhibited by bacterial frataxin even in this ex vivo condition. We also prove conclusively that iron acts as the effector of the reaction in prokaryotes. This study provides a new powerful tool for the study of iron sulfur cluster biogenesis.

FRIDAY, 20 de octubre de 2023, 12:00 h
Edificio I+D (Sala de Conferencias