Hindlimb Denervation Alters the Regulation of Autophagy and Mitophagy
Notice bibliographique
Résumé
During chronic muscle disuse, fibre atrophy occurs concomitantly with reductions in mitochondrial content and function. The reduction in organelle content is due, in part, to depressed mitochondrial biogenesis and elevations in intracellular degradation processes. The regulation of mitochondrial biogenesis has been studied extensively. However, the processes that underlie the degradation of mitochondria have yet to be fully elucidated. The breakdown of the organelle is due to a selective form of autophagy, termed mitophagy. When a mitochondrion becomes dysfunctional it dissociates from the mitochondrial network within the muscle and is subsequently degraded by lysosomes. The objective of this work is to better understand the processes of autophagy and mitophagy in the context of muscle disuse. Accordingly, we employed a hindlimb denervation protocol in which we unilaterally sectioned the peroneal nerve of one hindlimb, using the contralateral limb as a control in Sprague‐Dawley rats. Protein measurements of autophagy and mitochondrial content markers were made at 1, 3 and 7 days post‐denervation. We observed significant 25–30% (p<0.05) reductions in extensor digitorum longus (EDL) and tibialis anterior (TA) muscle mass by 7 days post‐denervation. Significant elevations in the autophagy proteins Tfeb, Beclin1 and ATG‐7 were also measured 7 days post denervation, while mitochondrial protein COX subunit‐IV and COX enzyme activity were reduced by 25% and 40%, respectively. However, SS and IMF mitochondrial respiratory capacity was diminished, accompanied by enhanced reactive oxygen species production, as early as 1–3 days following denervation. To investigate the early changes in autophagy and mitophagy flux that may explain the alterations in mitochondrial content and function, a subgroup of animals was treated with colchicine (4mg/kg/day) for 2 days to inhibit autophagic breakdown in response to 1 and 3 days of denervation. LC3‐II autophagy flux was increased as early as 1 and 3 days post‐denervation, but diminished by 7 days, in part as a result of a denervation‐induced increase in LC3‐II expression. Mitophagy flux was increased in parallel in SS mitochondria, and by 3 days in the IMF subfraction. These changes appeared to coincide with the declines in mitochondrial function, suggesting that although mitophagy is elevated, it is not sufficient to eliminate all of the dysfunctional organelles. Furthermore, the immediate elevations in autophagy/mitophagy flux at 1 and 3 days occurred prior to the upregulation of autophagy and lysosomal markers at 7 days post‐denervation, suggesting that the intrinsic activity of the autophagosomal breakdown pathway is sufficient in the early time course, but is subsequently upregulated to meet the demands of prolonged denervation. Support or Funding Information Supported by NSERC, Canada This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».