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Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle

Type 2 diabetes mellitus (T2D) affects millions of people worldwide and is one of the leading causes of morbidity and mortality. The skeletal muscle (SKM) is one of the most important tissues involved in maintaining glucose homeostasis and substrate oxidation, and it undergoes insulin resistance in...

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Autores principales: López-Soldado, Iliana, Torres, Adrian Gabriel, Ventura, Raúl, Martínez-Ruiz, Inma, Díaz-Ramos, Angels, Planet, Evarist, Cooper, Diane, Pazderska, Agnieszka, Wanic, Krzysztof, O'Hanlon, Declan, O'Gorman, Donal J., Carbonell, Teresa, de Pouplana, Lluís Ribas, Nolan, John J., Zorzano, Antonio, Hernández-Alvarez, María Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958393/
https://www.ncbi.nlm.nih.gov/pubmed/36796135
http://dx.doi.org/10.1016/j.redox.2023.102630
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author López-Soldado, Iliana
Torres, Adrian Gabriel
Ventura, Raúl
Martínez-Ruiz, Inma
Díaz-Ramos, Angels
Planet, Evarist
Cooper, Diane
Pazderska, Agnieszka
Wanic, Krzysztof
O'Hanlon, Declan
O'Gorman, Donal J.
Carbonell, Teresa
de Pouplana, Lluís Ribas
Nolan, John J.
Zorzano, Antonio
Hernández-Alvarez, María Isabel
author_facet López-Soldado, Iliana
Torres, Adrian Gabriel
Ventura, Raúl
Martínez-Ruiz, Inma
Díaz-Ramos, Angels
Planet, Evarist
Cooper, Diane
Pazderska, Agnieszka
Wanic, Krzysztof
O'Hanlon, Declan
O'Gorman, Donal J.
Carbonell, Teresa
de Pouplana, Lluís Ribas
Nolan, John J.
Zorzano, Antonio
Hernández-Alvarez, María Isabel
author_sort López-Soldado, Iliana
collection PubMed
description Type 2 diabetes mellitus (T2D) affects millions of people worldwide and is one of the leading causes of morbidity and mortality. The skeletal muscle (SKM) is one of the most important tissues involved in maintaining glucose homeostasis and substrate oxidation, and it undergoes insulin resistance in T2D. In this study, we identify the existence of alterations in the expression of mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in skeletal muscle from two different forms of T2D: early-onset type 2 diabetes (YT2) (onset of the disease before 30 years of age) and the classical form of the disease (OT2). GSEA analysis from microarray studies revealed the repression of mitochondrial mt-aaRSs independently of age, which was validated by real-time PCR assays. In agreement with this, a reduced expression of several encoding mt-aaRSs was also detected in skeletal muscle from diabetic (db/db) mice but not in obese ob/ob mice. In addition, the expression of the mt-aaRSs proteins most relevant in the synthesis of mitochondrial proteins, threonyl-tRNA, and leucyl-tRNA synthetases (TARS2 and LARS2) were also repressed in muscle from db/db mice. It is likely that these alterations participate in the reduced expression of proteins synthesized in the mitochondria detected in db/db mice. We also document an increased iNOS abundance in mitochondrial-enriched muscle fractions from diabetic mice that may inhibit aminoacylation of TARS2 and LARS2 by nitrosative stress. Our results indicate a reduced expression of mt-aaRSs in skeletal muscle from T2D patients, which may participate in the reduced expression of proteins synthesized in mitochondria. An enhanced mitochondrial iNOS could play a regulatory role in diabetes.
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spelling pubmed-99583932023-02-26 Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle López-Soldado, Iliana Torres, Adrian Gabriel Ventura, Raúl Martínez-Ruiz, Inma Díaz-Ramos, Angels Planet, Evarist Cooper, Diane Pazderska, Agnieszka Wanic, Krzysztof O'Hanlon, Declan O'Gorman, Donal J. Carbonell, Teresa de Pouplana, Lluís Ribas Nolan, John J. Zorzano, Antonio Hernández-Alvarez, María Isabel Redox Biol Articles from the Special Issue on Intersection between metabolism and redox biology in health and disease; Edited by Dr. Bradford Guy Hill and Dr. Rakesh Patel Type 2 diabetes mellitus (T2D) affects millions of people worldwide and is one of the leading causes of morbidity and mortality. The skeletal muscle (SKM) is one of the most important tissues involved in maintaining glucose homeostasis and substrate oxidation, and it undergoes insulin resistance in T2D. In this study, we identify the existence of alterations in the expression of mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) in skeletal muscle from two different forms of T2D: early-onset type 2 diabetes (YT2) (onset of the disease before 30 years of age) and the classical form of the disease (OT2). GSEA analysis from microarray studies revealed the repression of mitochondrial mt-aaRSs independently of age, which was validated by real-time PCR assays. In agreement with this, a reduced expression of several encoding mt-aaRSs was also detected in skeletal muscle from diabetic (db/db) mice but not in obese ob/ob mice. In addition, the expression of the mt-aaRSs proteins most relevant in the synthesis of mitochondrial proteins, threonyl-tRNA, and leucyl-tRNA synthetases (TARS2 and LARS2) were also repressed in muscle from db/db mice. It is likely that these alterations participate in the reduced expression of proteins synthesized in the mitochondria detected in db/db mice. We also document an increased iNOS abundance in mitochondrial-enriched muscle fractions from diabetic mice that may inhibit aminoacylation of TARS2 and LARS2 by nitrosative stress. Our results indicate a reduced expression of mt-aaRSs in skeletal muscle from T2D patients, which may participate in the reduced expression of proteins synthesized in mitochondria. An enhanced mitochondrial iNOS could play a regulatory role in diabetes. Elsevier 2023-02-08 /pmc/articles/PMC9958393/ /pubmed/36796135 http://dx.doi.org/10.1016/j.redox.2023.102630 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles from the Special Issue on Intersection between metabolism and redox biology in health and disease; Edited by Dr. Bradford Guy Hill and Dr. Rakesh Patel
López-Soldado, Iliana
Torres, Adrian Gabriel
Ventura, Raúl
Martínez-Ruiz, Inma
Díaz-Ramos, Angels
Planet, Evarist
Cooper, Diane
Pazderska, Agnieszka
Wanic, Krzysztof
O'Hanlon, Declan
O'Gorman, Donal J.
Carbonell, Teresa
de Pouplana, Lluís Ribas
Nolan, John J.
Zorzano, Antonio
Hernández-Alvarez, María Isabel
Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle
title Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle
title_full Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle
title_fullStr Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle
title_full_unstemmed Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle
title_short Decreased expression of mitochondrial aminoacyl-tRNA synthetases causes downregulation of OXPHOS subunits in type 2 diabetic muscle
title_sort decreased expression of mitochondrial aminoacyl-trna synthetases causes downregulation of oxphos subunits in type 2 diabetic muscle
topic Articles from the Special Issue on Intersection between metabolism and redox biology in health and disease; Edited by Dr. Bradford Guy Hill and Dr. Rakesh Patel
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958393/
https://www.ncbi.nlm.nih.gov/pubmed/36796135
http://dx.doi.org/10.1016/j.redox.2023.102630
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