Biallelic loss of molecular chaperone molecule AIP results in a novel severe multisystem disease defined by defective proteostasis
Authors list
Márta Korbonits Xian Wang Sayka Barry Chung Thong Lim Oniz Suleyman Stefano De Tito Nazia Uddin Maria Lillina Vignola Charlotte Hall Laura Perna J Paul Chapple Gabor Czbik Sian M Henson Valle Morales Katiuscia Bianchi Viðar Örn Eðvarðsson Kristján Ari Ragnarsson Viktoría Eir Kristinsdóttir Anne Debeer Yoeri Sleyp Rena Zinchenko Glenn Anderson Michael Duchen Kritarth Singh Chih Yao Chung Yu Yuan Sandip Patel Ezra Aksoy Artem O Borovikov Hans Tómas Björnsson Hilde Van Esch Sharon Tooze Caroline Brennan Oliver Haworth
Toggle all authors (34)
This article is a preprint. Preprints have not been peer-reviewed.
You can read more about preprints.
Abstract
Children born with deleterious biallelic variants of the chaperone aryl hydrocarbon receptor interacting protein (AIP) have a novel pediatric metabolic disease presenting a severe, complex clinical phenotype characterized by failure to develop following birth. Analysis of Aip knockout mouse embryonic fibroblasts and patient-derived dermal fibroblasts revealed that AIP was required to support proteostasis; including proteasome activity, induction of autophagy and lysosome function. aip knockout zebrafish, recapitulated the phenotype of the children; dying at an early stage of development when autophagy is required to adapt to periods of starvation. Our results demonstrate that AIP plays a crucial role in initiating autophagy and maintaining proteostasis in vitro and in vivo.
Details
Archive
bioRxiv
Available online
Publication date
Keywords
Type of publication
