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Model organisms in POLG-related disorders: insights from yeast to multicellular systems

Title: Model organisms in POLG-related disorders: insights from yeast to multicellular systems
Authors: Casas, Raquel Brañas; Risato, Giovanni; Zuppardo, Alessandro; Viscomi, Carlo; Argenton, Francesco; Doimo, Mara; Facchinello, Nicola; Tiso, Natascia
Contributors: Casas, Raquel Braña; Risato, Giovanni; Zuppardo, Alessandro; Viscomi, Carlo; Argenton, Francesco; Doimo, Mara; Facchinello, Nicola; Tiso, Natascia
Publication Year: 2026
Collection: Padua Research Archive (IRIS - Università degli Studi di Padova)
Subject Terms: POLG; Saccharomyces cerevisiae; Caenorhabditis elegans; Drosophila melanogaster; Mus musculus; Danio rerio; drug screening
Description: Mitochondrial genetic diseases are complex disorders that impair cellular energy production, leading to diverse clinical manifestations across multiple organ systems. These diseases arise from mutations in either mitochondrial DNA or nuclear DNA. Among nuclear DNA-related cases, mutations in POLG and POLG2, which encode subunits of mitochondrial DNA polymerase γ, are particularly significant, causing conditions such as Alpers-Huttenlocher syndrome and progressive external ophthalmoplegia. Model organisms have been instrumental in elucidating POLG-related disease mechanisms and advancing therapeutic strategies. Saccharomyces cerevisiae (budding yeast) provided insights into fundamental mitochondrial functions, while Caenorhabditis elegans (roundworm) helped explore POLG's roles in multicellular organisms. Drosophila melanogaster (fruit fly) has been pivotal in studying neurological aspects, and Mus musculus (mouse) models contributed to understanding systemic effects in mammals. Recently, Danio rerio (zebrafish) has emerged as a promising vertebrate model for drug screening, due to its optical transparency and genetic tractability. Each model system offers unique advantages, collectively bridging the gap between basic research and clinical applications. This review will examine in vivo models used in POLG disorder research, highlighting their contributions to understanding disease mechanisms and therapeutic advancements.
Document Type: article in journal/newspaper
File Description: ELETTRONICO
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/41453949; journal:CELL DEATH & DISEASE; https://hdl.handle.net/11577/3571678
DOI: 10.1038/s41419-025-08366-6
Availability: https://hdl.handle.net/11577/3571678; https://doi.org/10.1038/s41419-025-08366-6; https://www.nature.com/articles/s41419-025-08366-6
Rights: info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.1C55F13E
Database: BASE