Ragopathies and the Rising Influence of RagGTPases on Human Diseases

Authors

Irene Sambri
Marco Ferniani
Andrea Ballabio

Publication Date

7-10-2024

Journal

Nature Communications

DOI

10.1038/s41467-024-50034-4

PMID

38987251

PMCID

PMC11237164

PubMedCentral® Posted Date

7-10-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Mutation, Neoplasms, Mechanistic Target of Rapamycin Complex 1, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Animals, Cataract, Cardiomyopathy, Dilated, Mechanisms of disease, Preclinical research, Gene regulation

Abstract

RagGTPases (Rags) play an essential role in the regulation of cell metabolism by controlling the activities of both mechanistic target of rapamycin complex 1 (mTORC1) and Transcription factor EB (TFEB). Several diseases, herein named ragopathies, are associated to Rags dysfunction. These diseases may be caused by mutations either in genes encoding the Rags, or in their upstream regulators. The resulting phenotypes may encompass a variety of clinical features such as cataract, kidney tubulopathy, dilated cardiomyopathy and several types of cancer. In this review, we focus on the key clinical, molecular and physio-pathological features of ragopathies, aiming to shed light on their underlying mechanisms.