Alterations in mitochondrial fission, fusion, and mitophagic protein expression in the gastrocnemius of mice after a sciatic nerve transection

Graham, Zachary A.; Harlow, Lauren; Bauman, William A.; Cardozo, Christopher P.

doi:10.1002/mus.26197

Cited by 18 publications

(10 citation statements)

References 55 publications

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“…The dynamic control of the mitochondrial network in skeletal muscle fibers is regulated by the balance of mitochondrial biogenesis, fusion, and fission [26,27]. For example, muscle inactivity resulting from denervation is associated with changes in the expression of key fission and fusion proteins that results in the disruption of the mitochondrial network [78]. Similar findings have been reported in numerous other forms of muscle inactivity (reviewed in [25,27,79]).…”

Section: Mitochondrial Dysfunction Resulting In Increased Mitochondrial Ros Emission Promotes Inactivity-induced Muscle Atrophymentioning

confidence: 67%

Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Hyatt

Powers

2021

Antioxidants

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Skeletal muscle is the most abundant tissue in the body and is required for numerous vital functions, including breathing and locomotion. Notably, deterioration of skeletal muscle mass is also highly correlated to mortality in patients suffering from chronic diseases (e.g., cancer). Numerous conditions can promote skeletal muscle wasting, including several chronic diseases, cancer chemotherapy, aging, and prolonged inactivity. Although the mechanisms responsible for this loss of muscle mass is multifactorial, mitochondrial dysfunction is predicted to be a major contributor to muscle wasting in various conditions. This systematic review will highlight the biochemical pathways that have been shown to link mitochondrial dysfunction to skeletal muscle wasting. Importantly, we will discuss the experimental evidence that connects mitochondrial dysfunction to muscle wasting in specific diseases (i.e., cancer and sepsis), aging, cancer chemotherapy, and prolonged muscle inactivity (e.g., limb immobilization). Finally, in hopes of stimulating future research, we conclude with a discussion of important future directions for research in the field of muscle wasting.

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Section: Mitochondrial Dysfunction Resulting In Increased Mitochondrial Ros Emission Promotes Inactivity-induced Muscle Atrophymentioning

confidence: 67%

Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Hyatt

Powers

2021

Antioxidants

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“…Furthermore, prolonged sedentarism or aging induced profission phenotypes, suggesting a relationship between skeletal muscle oxidative capacity and mitochondrial dynamics. Activation of fission and inhibition of fusion proteins have additionally been reported in muscle denervation models, further strengthening this notion . However, generalizability of these findings is limited due to lack of normalization to changes in mitochondrial content.…”

Section: Discussionmentioning

confidence: 68%

Exercise training remodels human skeletal muscle mitochondrial fission and fusion machinery towards a pro‐elongation phenotype

et al. 2018

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Aims: Mitochondria exist as a morphologically plastic network driven by cellular bioenergetic demand. Induction of fusion and fission machinery allows the organelle to regulate quality control and substrate flux. Physiological stressors promote fragmentation of the mitochondrial network, a process implicated in the onset of metabolic disease, including type 2 diabetes and obesity. It is well-known that exercise training improves skeletal muscle mitochondrial volume, number, and density. However, the effect of exercise training on muscle mitochondrial dynamics remains unclear. Methods: Ten sedentary adults (65.8 ± 4.6 years; 34.3 ± 2.4 kg/m 2 ) underwent 12 weeks of supervised aerobic exercise training (5 day/wk, 85% of HR MAX ).Body composition, cardio-metabolic testing, hyperinsulinaemic-euglycaemic clamps, and skeletal muscle biopsies were performed before and after training. MFN1, MFN2, OPA1, OMA1, FIS1, Parkin, PGC-1α, and HSC70 protein expression was assessed via Western blot. Results: Exercise training led to improvements in insulin sensitivity, aerobic capacity, and fat oxidation (all P < 0.01), as well as reductions in body weight, BMI, fat mass and fasting glucose (all P < 0.001). When normalized for changes in mitochondrial content, exercise reduced skeletal muscle FIS1 and Parkin (P < 0.05), while having no significant effect on MFN1, MFN2, OPA1, and OMA1 expression. Exercise also improved the ratio of fusion to fission proteins (P < 0.05), which positively correlated with improvements in glucose disposal (r 2 = 0.59, P < 0.05). Conclusions: Exercise training alters the expression of mitochondrial fusion and fission proteins, promoting a more fused, tubular network. These changes may contribute to the improvements in insulin sensitivity and substrate utilization that are observed after exercise training.

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“…Methods for SDS‐PAGE and Western immunoblotting have been published previously (Graham, Harlow, & Bauman, ). Briefly, for whole muscle lysate analysis, ~30 mg of the left soleus was homogenized by an automated bead homogenizer using a cocktail of 1:10 w/v of 1x RIPA buffer supplemented with phosphatase and protease inhibitors.…”

Section: Methodsmentioning

confidence: 99%

Contusion spinal cord injury upregulates p53 protein expression in rat soleus muscle at multiple timepoints but not key senescence cytokines

et al. 2020

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To determine whether muscle disuse after a spinal cord injury (SCI) produces elevated markers of cellular senescence and induces markers of the senescence‐associated secretory phenotypes (SASPs) in paralyzed skeletal muscle. Four‐month‐old male Sprague‐Dawley rats received a moderate‐severe (250 kiloDyne) T‐9 contusion SCI or Sham surgery and were monitored over 2 weeks, and 1‐, 2‐, or 3 months. Animals were sacrificed via isoflurane overdose and terminal exsanguination and the soleus was carefully excised and snap frozen. Protein expression of senescence markers p53, p27, and p16 was determined from whole soleus lysates using Western immunoblotting and RT‐qPCR was used to determine the soleus gene expression of IL‐1α, IL‐1β, IL‐6, CXCL1, and TNFα. SCI soleus muscle displayed 2‐ to 3‐fold higher total p53 protein expression at 2 weeks, and at 1 and 2 months when compared with Sham. p27 expression was stable across all groups and timepoints. p16 protein expression was lower at 3 months in SCI versus Sham, but not earlier timepoints. Gene expression was relatively stable between groups at 2 weeks. There were Surgery x Time interaction effects for IL‐6 and TNFα mRNA expression but not for IL‐1α, IL‐1β, or CXCL1. There were no main effects for time or surgery for IL‐1α, IL‐1β, or CXCL1, but targeted t tests showed reductions in IL‐1α and CXCL1 in SCI animals compared to Sham at 3 months and IL‐1β was reduced in SCI animals compared to Sham animals at the 2‐month timepoint. The elevation in p53 does not appear consistent with the induction of SASP because mRNA expression of cytokines associated with senescence was not uniformly upregulated and, in some instances, was downregulated in the early chronic phase of SCI.

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Alterations in mitochondrial fission, fusion, and mitophagic protein expression in the gastrocnemius of mice after a sciatic nerve transection

Cited by 18 publications

References 55 publications

Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Exercise training remodels human skeletal muscle mitochondrial fission and fusion machinery towards a pro‐elongation phenotype

Contusion spinal cord injury upregulates p53 protein expression in rat soleus muscle at multiple timepoints but not key senescence cytokines

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