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Article ; Online: Editorial: Highlights in Autophagy-From Basic Mechanisms to Human Disorder Treatments.

Lin, Pei-Hui / Combaret, Lydie

2023 Volume 12, Issue 1

Abstract: Autophagy is an evolutionarily conserved catabolic process and represents a field of research that is constantly growing [ ... ]. ...

Abstract	Autophagy is an evolutionarily conserved catabolic process and represents a field of research that is constantly growing [...].
MeSH term(s)	Humans ; Autophagy
Language	English
Publishing date	2023-01-03
Publishing country	Switzerland
Document type	Editorial ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12010188
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Article ; Online: Ubiquitin Ligases at the Heart of Skeletal Muscle Atrophy Control.

Peris-Moreno, Dulce / Cussonneau, Laura / Combaret, Lydie / Polge, Cécile / Taillandier, Daniel

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 2

Abstract: Skeletal muscle loss is a detrimental side-effect of numerous chronic diseases that dramatically increases mortality and morbidity. The alteration of protein homeostasis is generally due to increased protein breakdown while, protein synthesis may also be ...

Abstract	Skeletal muscle loss is a detrimental side-effect of numerous chronic diseases that dramatically increases mortality and morbidity. The alteration of protein homeostasis is generally due to increased protein breakdown while, protein synthesis may also be down-regulated. The ubiquitin proteasome system (UPS) is a master regulator of skeletal muscle that impacts muscle contractile properties and metabolism through multiple levers like signaling pathways, contractile apparatus degradation, etc. Among the different actors of the UPS, the E3 ubiquitin ligases specifically target key proteins for either degradation or activity modulation, thus controlling both pro-anabolic or pro-catabolic factors. The atrogenes MuRF1/TRIM63 and MAFbx/Atrogin-1 encode for key E3 ligases that target contractile proteins and key actors of protein synthesis respectively. However, several other E3 ligases are involved upstream in the atrophy program, from signal transduction control to modulation of energy balance. Controlling E3 ligases activity is thus a tempting approach for preserving muscle mass. While indirect modulation of E3 ligases may prove beneficial in some situations of muscle atrophy, some drugs directly inhibiting their activity have started to appear. This review summarizes the main signaling pathways involved in muscle atrophy and the E3 ligases implicated, but also the molecules potentially usable for future therapies.
MeSH term(s)	Animals ; Humans ; Muscular Atrophy/enzymology ; Muscular Atrophy/physiopathology ; Protein Biosynthesis ; Signal Transduction ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Ubiquitin ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2021-01-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26020407
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Article ; Online: A Single Bout of Ultra-Endurance Exercise Reveals Early Signs of Muscle Aging in Master Athletes.

Coudy-Gandilhon, Cécile / Gueugneau, Marine / Chambon, Christophe / Taillandier, Daniel / Combaret, Lydie / Polge, Cécile / Millet, Guillaume Y / Féasson, Léonard / Béchet, Daniel

International journal of molecular sciences

2022 Volume 23, Issue 7

Abstract: Middle-aged and master endurance athletes exhibit similar physical performance and long-term muscle adaptation to aerobic exercise. Nevertheless, we hypothesized that the short-term plasticity of the skeletal muscle might be distinctly altered for master ...

Abstract	Middle-aged and master endurance athletes exhibit similar physical performance and long-term muscle adaptation to aerobic exercise. Nevertheless, we hypothesized that the short-term plasticity of the skeletal muscle might be distinctly altered for master athletes when they are challenged by a single bout of prolonged moderate-intensity exercise. Six middle-aged (37Y) and five older (50Y) master highly-trained athletes performed a 24-h treadmill run (24TR).
MeSH term(s)	Aging/physiology ; Athletes ; Exercise/physiology ; Humans ; Middle Aged ; Muscle, Skeletal/physiology ; Physical Endurance/physiology
Language	English
Publishing date	2022-03-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23073713
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Article ; Online: Temporal regulation of transgene expression controlled by amino acid availability in human T cells.

Dougé, Aurore / Vituret, Cyrielle / Carraro, Valérie / Parry, Laurent / Coudy-Gandilhon, Cécile / Lemal, Richard / Combaret, Lydie / Maurin, Anne-Catherine / Averous, Julien / Jousse, Céline / Bay, Jacques-Olivier / Verrelle, Pierre / Fafournoux, Pierre / Bruhat, Alain / Rouzaire, Paul

HLA

2023 Volume 103, Issue 1, Page(s) e15252

Abstract: T cell therapy strategies, from allogeneic stem cell transplantation toward genetically-modified T cells infusion, develop powerful anti-tumor effects but are often accompanied by side effects and their efficacy remains sometimes to be improved. It ... ...

Abstract	T cell therapy strategies, from allogeneic stem cell transplantation toward genetically-modified T cells infusion, develop powerful anti-tumor effects but are often accompanied by side effects and their efficacy remains sometimes to be improved. It therefore appears important to provide a flexible and easily reversible gene expression regulation system to control T cells activity. We developed a gene expression regulation technology that exploits the physiological GCN2-ATF4 pathway's ability to induce gene expression in T cells in response to one essential amino acid deficiency. We first demonstrated the functionality of NUTRIREG in human T cells by transient expression of reporter genes. We then validated that NUTRIREG can be used in human T cells to transiently express a therapeutic gene such as IL-10. Overall, our results represent a solid basis for the promising use of NUTRIREG to regulate transgene expression in human T cells in a reversible way, and more generally for numerous preventive or curative therapeutic possibilities in cellular immunotherapy strategies.
MeSH term(s)	Humans ; Graft vs Host Disease/prevention & control ; Transplantation, Homologous ; Amino Acids ; Alleles ; Hematopoietic Stem Cell Transplantation/adverse effects ; T-Lymphocytes ; Transgenes
Chemical Substances	Amino Acids
Language	English
Publishing date	2023-10-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2845111-9
ISSN	2059-2310 ; 2059-2302
ISSN (online)	2059-2310
ISSN	2059-2302
DOI	10.1111/tan.15252
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Article ; Online: Targeting the gut to prevent and counteract metabolic disorders and pathologies during aging.

Milenkovic, Dragan / Capel, Frédéric / Combaret, Lydie / Comte, Blandine / Dardevet, Dominique / Evrard, Bertrand / Guillet, Christelle / Monfoulet, Laurent-Emmanuel / Pinel, Alexandre / Polakof, Sergio / Pujos-Guillot, Estelle / Rémond, Didier / Wittrant, Yohann / Savary-Auzeloux, Isabelle

Critical reviews in food science and nutrition

2022 Volume 63, Issue 32, Page(s) 11185–11210

Abstract: Impairment of gut function is one of the explanatory mechanisms of health status decline in elderly population. These impairments involve a decline in gut digestive physiology, metabolism and immune status, and associated to that, changes in composition ... ...

Abstract	Impairment of gut function is one of the explanatory mechanisms of health status decline in elderly population. These impairments involve a decline in gut digestive physiology, metabolism and immune status, and associated to that, changes in composition and function of the microbiota it harbors. Continuous deteriorations are generally associated with the development of systemic dysregulations and ultimately pathologies that can worsen the initial health status of individuals. All these alterations observed at the gut level can then constitute a wide range of potential targets for development of nutritional strategies that can impact gut tissue or associated microbiota pattern. This can be key, in a preventive manner, to limit gut functionality decline, or in a curative way to help maintaining optimum nutrients bioavailability in a context on increased requirements, as frequently observed in pathological situations. The aim of this review is to give an overview on the alterations that can occur in the gut during aging and lead to the development of altered function in other tissues and organs, ultimately leading to the development of pathologies. Subsequently is discussed how nutritional strategies that target gut tissue and gut microbiota can help to avoid or delay the occurrence of aging-related pathologies.
MeSH term(s)	Humans ; Aged ; Aging/physiology ; Metabolic Diseases/prevention & control ; Microbiota ; Gastrointestinal Microbiome/physiology ; Nutritive Value
Language	English
Publishing date	2022-06-22
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	1037504-1
ISSN	1549-7852 ; 1040-8398
ISSN (online)	1549-7852
ISSN	1040-8398
DOI	10.1080/10408398.2022.2089870
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Article ; Online: Activation of the eIF2α-ATF4 Pathway by Chronic Paracetamol Treatment Is Prevented by Dietary Supplementation with Cysteine.

Carraro, Valérie / Combaret, Lydie / Coudy-Gandilhon, Cécile / Parry, Laurent / Averous, Julien / Maurin, Anne-Catherine / Jousse, Céline / Voyard, Guillaume / Fafournoux, Pierre / Papet, Isabelle / Bruhat, Alain

International journal of molecular sciences

2022 Volume 23, Issue 13

Abstract: Chronic treatment with acetaminophen (APAP) induces cysteine (Cys) and glutathione (GSH) deficiency which leads to adverse metabolic effects including muscle atrophy. Mammalian cells respond to essential amino acid deprivation through the phosphorylation ...

Abstract	Chronic treatment with acetaminophen (APAP) induces cysteine (Cys) and glutathione (GSH) deficiency which leads to adverse metabolic effects including muscle atrophy. Mammalian cells respond to essential amino acid deprivation through the phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α). Phosphorylated eIF2α leads to the recruitment of activating transcription factor 4 (ATF4) to specific CCAAT/enhancer-binding protein-ATF response element (CARE) located in the promoters of target genes. Our purpose was to study the activation of the eIF2α-ATF4 pathway in response to APAP-induced Cys deficiency, as well as the potential contribution of the eIF2α kinase GCN2 and the effect of dietary supplementation with Cys. Our results showed that chronic treatment with APAP activated both GCN2 and PERK eIF2α kinases and downstream target genes in the liver. Activation of the eIF2α-ATF4 pathway in skeletal muscle was accompanied by muscle atrophy even in the absence of GCN2. The dietary supplementation with cysteine reversed APAP-induced decreases in plasma-free Cys, liver GSH, muscle mass, and muscle GSH. Our new findings demonstrate that dietary Cys supplementation also reversed the APAP-induced activation of GCN2 and PERK and downstream ATF4-target genes in the liver.
MeSH term(s)	Acetaminophen/adverse effects ; Activating Transcription Factor 4/genetics ; Activating Transcription Factor 4/metabolism ; Animals ; Cysteine/metabolism ; Dietary Supplements ; Eukaryotic Initiation Factor-2/metabolism ; Glutathione/metabolism ; Mammals/metabolism ; Muscular Atrophy/chemically induced ; Phosphorylation ; eIF-2 Kinase/genetics ; eIF-2 Kinase/metabolism
Chemical Substances	Eukaryotic Initiation Factor-2 ; Activating Transcription Factor 4 (145891-90-3) ; Acetaminophen (362O9ITL9D) ; eIF-2 Kinase (EC 2.7.11.1) ; Glutathione (GAN16C9B8O) ; Cysteine (K848JZ4886)
Language	English
Publishing date	2022-06-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23137196
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Article ; Online: Mitophagy and Mitochondria Biogenesis Are Differentially Induced in Rat Skeletal Muscles during Immobilization and/or Remobilization.

Deval, Christiane / Calonne, Julie / Coudy-Gandilhon, Cécile / Vazeille, Emilie / Bechet, Daniel / Polge, Cécile / Taillandier, Daniel / Attaix, Didier / Combaret, Lydie

International journal of molecular sciences

2020 Volume 21, Issue 10

Abstract: Mitochondria alterations are a classical feature of muscle immobilization, and autophagy is required for the elimination of deficient mitochondria (mitophagy) and the maintenance of muscle mass. We focused on the regulation of mitochondrial quality ... ...

Abstract	Mitochondria alterations are a classical feature of muscle immobilization, and autophagy is required for the elimination of deficient mitochondria (mitophagy) and the maintenance of muscle mass. We focused on the regulation of mitochondrial quality control during immobilization and remobilization in rat gastrocnemius (GA) and tibialis anterior (TA) muscles, which have very different atrophy and recovery kinetics. We studied mitochondrial biogenesis, dynamic, movement along microtubules, and addressing to autophagy. Our data indicated that mitochondria quality control adapted differently to immobilization and remobilization in GA and TA muscles. Data showed i) a disruption of mitochondria dynamic that occurred earlier in the immobilized TA, ii) an overriding role of mitophagy that involved Parkin-dependent and/or independent processes during immobilization in the GA and during remobilization in the TA, and iii) increased mitochondria biogenesis during remobilization in both muscles. This strongly emphasized the need to consider several muscle groups to study the mechanisms involved in muscle atrophy and their ability to recover, in order to provide broad and/or specific clues for the development of strategies to maintain muscle mass and improve the health and quality of life of patients.
MeSH term(s)	Animals ; Male ; Mitochondria, Muscle/metabolism ; Mitophagy ; Motor Activity ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/physiology ; Muscle, Skeletal/physiopathology ; Muscular Atrophy/metabolism ; Rats ; Rats, Wistar ; Restraint, Physical/adverse effects
Language	English
Publishing date	2020-05-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21103691
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Article ; Online: UBE2L3, a Partner of MuRF1/TRIM63, Is Involved in the Degradation of Myofibrillar Actin and Myosin.

Peris-Moreno, Dulce / Malige, Mélodie / Claustre, Agnès / Armani, Andrea / Coudy-Gandilhon, Cécile / Deval, Christiane / Béchet, Daniel / Fafournoux, Pierre / Sandri, Marco / Combaret, Lydie / Taillandier, Daniel / Polge, Cécile

Cells

2021 Volume 10, Issue 8

Abstract: The ubiquitin proteasome system (UPS) is the main player of skeletal muscle wasting, a common characteristic of many diseases (cancer, etc.) that negatively impacts treatment and life prognosis. Within the UPS, the E3 ligase MuRF1/TRIM63 targets for ... ...

Abstract	The ubiquitin proteasome system (UPS) is the main player of skeletal muscle wasting, a common characteristic of many diseases (cancer, etc.) that negatively impacts treatment and life prognosis. Within the UPS, the E3 ligase MuRF1/TRIM63 targets for degradation several myofibrillar proteins, including the main contractile proteins alpha-actin and myosin heavy chain (MHC). We previously identified five E2 ubiquitin-conjugating enzymes interacting with MuRF1, including UBE2L3/UbcH7, that exhibited a high affinity for MuRF1 (K
MeSH term(s)	Actins/metabolism ; Animals ; Cell Line ; Dexamethasone/pharmacology ; Histocompatibility Antigens Class II/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Muscle Fibers, Skeletal/cytology ; Muscle Fibers, Skeletal/drug effects ; Muscle Fibers, Skeletal/metabolism ; Muscle Proteins/metabolism ; Muscular Atrophy/metabolism ; Muscular Atrophy/pathology ; Protein Binding ; RNA Interference ; RNA, Small Interfering/metabolism ; Tripartite Motif Proteins/metabolism ; Ubiquitin-Conjugating Enzymes/antagonists & inhibitors ; Ubiquitin-Conjugating Enzymes/genetics ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Actins ; Histocompatibility Antigens Class II ; Muscle Proteins ; RNA, Small Interfering ; Tripartite Motif Proteins ; Dexamethasone (7S5I7G3JQL) ; Ube2l3 protein, mouse (EC 2.3.2.23) ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; Trim63 protein, mouse (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2021-08-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10081974
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Article ; Online: Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men.

Gueugneau, Marine / Coudy-Gandilhon, Cécile / Chambon, Christophe / Verney, Julien / Taillandier, Daniel / Combaret, Lydie / Polge, Cécile / Walrand, Stéphane / Roche, Frédéric / Barthélémy, Jean-Claude / Féasson, Léonard / Béchet, Daniel

International journal of molecular sciences

2021 Volume 22, Issue 8

Abstract: 1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be ... ...

Abstract	(1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified. Herein we performed omic profiling to decipher in muscle which dominating processes are associated with healthy aging and metabolic syndrome in old men. (2) Methods: This study included 15 healthy young, 15 healthy old, and 9 old men with metabolic syndrome. Old men were selected from a well-characterized cohort, and each vastus lateralis biopsy was used to combine global transcriptomic and proteomic analyses. (3) Results: Over-representation analysis of differentially expressed genes (ORA) and functional class scoring of pathways (FCS) indicated that healthy aging was mainly associated with upregulations of apoptosis and immune function and downregulations of glycolysis and protein catabolism. ORA and FCS indicated that with metabolic syndrome the dominating biological processes were upregulation of proteolysis and downregulation of oxidative phosphorylation. Proteomic profiling matched 586 muscle proteins between individuals. The proteome of healthy aging revealed modifications consistent with a fast-to-slow transition and downregulation of glycolysis. These transitions were reduced with metabolic syndrome, which was more associated with alterations in NADH/NAD
MeSH term(s)	Animals ; Glycolysis/genetics ; Glycolysis/physiology ; Humans ; Metabolic Syndrome/genetics ; Metabolic Syndrome/metabolism ; Muscle, Skeletal/metabolism ; Proteomics/methods ; Sarcopenia/genetics ; Sarcopenia/metabolism ; Transcriptome/genetics
Language	English
Publishing date	2021-04-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22084205
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Article ; Online: High-Intensity Interval Training and α-Linolenic Acid Supplementation Improve DHA Conversion and Increase the Abundance of Gut Mucosa-Associated

Plissonneau, Claire / Capel, Frederic / Chassaing, Benoit / Dupuit, Marine / Maillard, Florie / Wawrzyniak, Ivan / Combaret, Lydie / Dutheil, Frederic / Etienne, Monique / Mairesse, Guillaume / Chesneau, Guillaume / Barnich, Nicolas / Boisseau, Nathalie

Nutrients

2021 Volume 13, Issue 3

Abstract: Obesity, a major public health problem, is the consequence of an excess of body fat and biological alterations in the adipose tissue. Our aim was to determine whether high-intensity interval training (HIIT) and/or α-linolenic acid supplementation (to ... ...

Abstract	Obesity, a major public health problem, is the consequence of an excess of body fat and biological alterations in the adipose tissue. Our aim was to determine whether high-intensity interval training (HIIT) and/or α-linolenic acid supplementation (to equilibrate the n-6/n-3 polyunsaturated fatty acids (PUFA) ratio) might prevent obesity disorders, particularly by modulating the mucosa-associated microbiota. Wistar rats received a low fat diet (LFD; control) or high fat diet (HFD) for 16 weeks to induce obesity. Then, animals in the HFD group were divided in four groups: HFD (control), HFD + linseed oil (LO), HFD + HIIT, HFD + HIIT + LO. In the HIIT groups, rats ran on a treadmill, 4 days.week
Language	English
Publishing date	2021-02-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu13030788
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