Cargando…

Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration

Nicotinamide riboside kinases (NRKs) control the conversion of dietary Nicotinamide Riboside (NR) to NAD(+), but little is known about their contribution to endogenous NAD(+) turnover and muscle plasticity during skeletal muscle growth and remodeling. Using NRK1/2 double KO (NRKdKO) mice, we investi...

Descripción completa

Detalles Bibliográficos
Autores principales: Sonntag, Tanja, Ancel, Sara, Karaz, Sonia, Cichosz, Paulina, Jacot, Guillaume, Giner, Maria Pilar, Sanchez-Garcia, José Luis, Pannérec, Alice, Moco, Sofia, Sorrentino, Vincenzo, Cantó, Carles, Feige, Jérôme N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682158/
https://www.ncbi.nlm.nih.gov/pubmed/36438552
http://dx.doi.org/10.3389/fcell.2022.1049653
_version_ 1784834787579527168
author Sonntag, Tanja
Ancel, Sara
Karaz, Sonia
Cichosz, Paulina
Jacot, Guillaume
Giner, Maria Pilar
Sanchez-Garcia, José Luis
Pannérec, Alice
Moco, Sofia
Sorrentino, Vincenzo
Cantó, Carles
Feige, Jérôme N.
author_facet Sonntag, Tanja
Ancel, Sara
Karaz, Sonia
Cichosz, Paulina
Jacot, Guillaume
Giner, Maria Pilar
Sanchez-Garcia, José Luis
Pannérec, Alice
Moco, Sofia
Sorrentino, Vincenzo
Cantó, Carles
Feige, Jérôme N.
author_sort Sonntag, Tanja
collection PubMed
description Nicotinamide riboside kinases (NRKs) control the conversion of dietary Nicotinamide Riboside (NR) to NAD(+), but little is known about their contribution to endogenous NAD(+) turnover and muscle plasticity during skeletal muscle growth and remodeling. Using NRK1/2 double KO (NRKdKO) mice, we investigated the influence of NRKs on NAD(+) metabolism and muscle homeostasis, and on the response to neurogenic muscle atrophy and regeneration following muscle injury. Muscles from NRKdKO animals have altered nicotinamide (NAM) salvage and a decrease in mitochondrial content. In single myonuclei RNAseq of skeletal muscle, NRK2 mRNA expression is restricted to type IIx muscle fibers, and perturbed NAD(+) turnover and mitochondrial metabolism shifts the fiber type composition of NRKdKO muscle to fast glycolytic IIB fibers. NRKdKO does not influence muscle atrophy during denervation but alters muscle repair after myofiber injury. During regeneration, muscle stem cells (MuSCs) from NRKdKO animals hyper-proliferate but fail to differentiate. NRKdKO also alters the recovery of NAD(+) during muscle regeneration as well as mitochondrial adaptations and extracellular matrix remodeling required for tissue repair. These metabolic perturbations result in a transient delay of muscle regeneration which normalizes during myofiber maturation at late stages of regeneration via over-compensation of anabolic IGF1-Akt signaling. Altogether, we demonstrate that NAD(+) synthesis controls mitochondrial metabolism and fiber type composition via NRK1/2 and is rate-limiting for myogenic commitment and mitochondrial maturation during skeletal muscle repair.
format Online
Article
Text
id pubmed-9682158
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96821582022-11-24 Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration Sonntag, Tanja Ancel, Sara Karaz, Sonia Cichosz, Paulina Jacot, Guillaume Giner, Maria Pilar Sanchez-Garcia, José Luis Pannérec, Alice Moco, Sofia Sorrentino, Vincenzo Cantó, Carles Feige, Jérôme N. Front Cell Dev Biol Cell and Developmental Biology Nicotinamide riboside kinases (NRKs) control the conversion of dietary Nicotinamide Riboside (NR) to NAD(+), but little is known about their contribution to endogenous NAD(+) turnover and muscle plasticity during skeletal muscle growth and remodeling. Using NRK1/2 double KO (NRKdKO) mice, we investigated the influence of NRKs on NAD(+) metabolism and muscle homeostasis, and on the response to neurogenic muscle atrophy and regeneration following muscle injury. Muscles from NRKdKO animals have altered nicotinamide (NAM) salvage and a decrease in mitochondrial content. In single myonuclei RNAseq of skeletal muscle, NRK2 mRNA expression is restricted to type IIx muscle fibers, and perturbed NAD(+) turnover and mitochondrial metabolism shifts the fiber type composition of NRKdKO muscle to fast glycolytic IIB fibers. NRKdKO does not influence muscle atrophy during denervation but alters muscle repair after myofiber injury. During regeneration, muscle stem cells (MuSCs) from NRKdKO animals hyper-proliferate but fail to differentiate. NRKdKO also alters the recovery of NAD(+) during muscle regeneration as well as mitochondrial adaptations and extracellular matrix remodeling required for tissue repair. These metabolic perturbations result in a transient delay of muscle regeneration which normalizes during myofiber maturation at late stages of regeneration via over-compensation of anabolic IGF1-Akt signaling. Altogether, we demonstrate that NAD(+) synthesis controls mitochondrial metabolism and fiber type composition via NRK1/2 and is rate-limiting for myogenic commitment and mitochondrial maturation during skeletal muscle repair. Frontiers Media S.A. 2022-11-09 /pmc/articles/PMC9682158/ /pubmed/36438552 http://dx.doi.org/10.3389/fcell.2022.1049653 Text en Copyright © 2022 Sonntag, Ancel, Karaz, Cichosz, Jacot, Giner, Sanchez-Garcia, Pannérec, Moco, Sorrentino, Cantó and Feige. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Sonntag, Tanja
Ancel, Sara
Karaz, Sonia
Cichosz, Paulina
Jacot, Guillaume
Giner, Maria Pilar
Sanchez-Garcia, José Luis
Pannérec, Alice
Moco, Sofia
Sorrentino, Vincenzo
Cantó, Carles
Feige, Jérôme N.
Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration
title Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration
title_full Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration
title_fullStr Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration
title_full_unstemmed Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration
title_short Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration
title_sort nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682158/
https://www.ncbi.nlm.nih.gov/pubmed/36438552
http://dx.doi.org/10.3389/fcell.2022.1049653
work_keys_str_mv AT sonntagtanja nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT ancelsara nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT karazsonia nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT cichoszpaulina nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT jacotguillaume nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT ginermariapilar nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT sanchezgarciajoseluis nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT pannerecalice nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT mocosofia nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT sorrentinovincenzo nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT cantocarles nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration
AT feigejeromen nicotinamideribosidekinasesregulateskeletalmusclefibertypespecificationandareratelimitingformetabolicadaptationsduringregeneration