The importance of mitochondrial quality control for maintaining skeletal muscle function across health span

Sligar, James; Debruin, Danielle A; Saner, Nicholas J.; Philp, Ashleigh M.; Philp, Andrew

doi:10.1152/ajpcell.00388.2021

Cited by 25 publications

(13 citation statements)

References 76 publications

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“…However, the translatory response of mitochondrial proteins tends to decline with age, suggesting a post-transcriptional block [ 144 ]. This observation is in line with the numerous studies showing reduced protein synthetic potential and quality control in aged muscle [ 16 , 24 , 25 , 31 , 32 , 33 , 34 , 35 ]. This in turn could be explained by the divergent muscle miRNA profile in aged men compared to young adults at baseline and post-exercise [ 69 ].…”

Section: Introductionsupporting

confidence: 89%

“…Multiple human and animal-based studies suggest that maintenance of mitochondrial quality control through exercise, nutritional or pharmacological interventions slows down the progression of sarcopenia and rate of functional decline [ 25 ]. Moreover, six weeks of isolated knee-extension endurance training enhanced the activity of the mitochondrial enzymes (citrate synthase, mitochondrial complexes I–IV) in the quadriceps muscle of young men independent of the mitochondrial volume and mtDNA content [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…Mitochondrial quality control plays a prominent role in sarcopenia [ 16 , 24 , 25 ]. Abnormally swollen mitochondria were observed in skeletal muscles of old mice despite the upregulated expression of autophagic proteins including p62, PARK-2, and DJ-1 suggesting impaired autophagy [ 53 ].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNAs as the Sentinels of Redox and Hypertrophic Signalling

Kolodziej

Burns

Goljanek‐Whysall

2022

IJMS

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Oxidative stress and inflammation are associated with skeletal muscle function decline with ageing or disease or inadequate exercise and/or poor diet. Paradoxically, reactive oxygen species and inflammatory cytokines are key for mounting the muscular and systemic adaptive responses to endurance and resistance exercise. Both ageing and lifestyle-related metabolic dysfunction are strongly linked to exercise redox and hypertrophic insensitivity. The adaptive inability and consequent exercise intolerance may discourage people from physical training resulting in a vicious cycle of under-exercising, energy surplus, chronic mitochondrial stress, accelerated functional decline and increased susceptibility to serious diseases. Skeletal muscles are malleable and dynamic organs, rewiring their metabolism depending on the metabolic or mechanical stress resulting in a specific phenotype. Endogenous RNA silencing molecules, microRNAs, are regulators of these metabolic/phenotypic shifts in skeletal muscles. Skeletal muscle microRNA profiles at baseline and in response to exercise have been observed to differ between adult and older people, as well as trained vs. sedentary individuals. Likewise, the circulating microRNA blueprint varies based on age and training status. Therefore, microRNAs emerge as key regulators of metabolic health/capacity and hormetic adaptability. In this narrative review, we summarise the literature exploring the links between microRNAs and skeletal muscle, as well as systemic adaptation to exercise. We expand a mathematical model of microRNA burst during adaptation to exercise through supporting data from the literature. We describe a potential link between the microRNA-dependent regulation of redox-signalling sensitivity and the ability to mount a hypertrophic response to exercise or nutritional cues. We propose a hypothetical model of endurance exercise-induced microRNA “memory cloud” responsible for establishing a landscape conducive to aerobic as well as anabolic adaptation. We suggest that regular aerobic exercise, complimented by a healthy diet, in addition to promoting mitochondrial health and hypertrophic/insulin sensitivity, may also suppress the glycolytic phenotype and mTOR signalling through miRNAs which in turn promote systemic metabolic health.

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Section: Introductionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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MicroRNAs as the Sentinels of Redox and Hypertrophic Signalling

Kolodziej

Burns

Goljanek‐Whysall

2022

IJMS

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“…[ 1 ] Mitochondria are the principal energy‐producing organelles in skeletal muscle cells, and their physiological role in antifatigue has expanded dramatically (i.e., metabolism, growth, or regeneration) over the past decade. [ 2 ] Physical fatigue generally manifests as a reversible decline in objective measures of performance, such as power, speed, and torque, after a bout of Ex. [ 3 ] Recent reports have identified fatigue as one of the most prevalent symptoms related to negative emotions such as worry, stress, anxiety, or stress.…”

Section: Introductionmentioning

confidence: 99%

Reshaped Gut Microbial Composition and Functions Associated with the Antifatigue Effect of Salidroside in Exercise Mice

Zhu

Shen²,

Wang

et al. 2023

Molecular Nutrition Food Res

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Scope Salidroside (SA) is an active compound derived from Rhodiola rosea and is widely used in healthcare foods. However, the underlying mechanism and its specific role in regulating the gut microbial community during exercise (Ex) remains unknown. Methods and results Mice are subjected to a weight‐loaded swimming test (WST) Ex to determine how gut microbiota affects the antifatigue activity of SA. The SA‐treated group mice (100 mg kg−1.bw.) display a significant increase in swimming time compared to the control group (26.2 versus 10.5 min, p < 0.01), as well as an increase in respiratory enzymatic activities after swimming. The respiratory enzymatic activities are significantly higher in the SA‐treated group than in the RS (regular rest) group after swimming. The bacteria profiles in the Ex + SA group change significantly with higher species diversity and abundance. Receiver operating characteristic (ROC) curves of Alistipes, Rikenellaceae, Parabacteroides, Candidatus Arthromitus, and Lactobacillus indicate a high diagnostic utility to distinguish SA treatment. Microbial function analysis shows that SA may improve Ex‐induced fatigue by modulating energy metabolism‐related processes. Conclusions SA demonstrates antifatigue effects on various levels of regulating energy metabolism and microbial composition, providing insights into the underlying mechanisms of SA as a natural prebiotic.

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“…Mitochondrial dysfunction may lead to metabolic disorders, loss of muscle mass and contractile dysfunction. Therefore, mitochondria have developed a series of mechanisms to maintain their homeostasis, including antioxidant machinery, fission and fusion, mitochondrial biogenesis, mitophagy ( 13 ) and the mitochondrial unfolded protein response (UPRmt) ( 14 ). Evidence suggests that insulin sensitivity in skeletal muscle is closely related to mitochondrial homeostasis.…”

Section: Introductionmentioning

confidence: 99%

The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats

Zhang

et al. 2023

Front. Endocrinol.

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IntroductionSkeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes mellitus. Skeletal muscle is a heterogeneous tissue composed of different muscle fiber types that contribute distinctly to IR development. Glucose transport shows more protection in slow-twitch muscles than in fast-twitch muscles during IR development, while the mechanisms involved remain unclear. Therefore, we investigated the role of the mitochondrial unfolded protein response (UPRmt) in the distinct resistance of two types of muscle in IR.MethodsMale Wistar rats were divided into high-fat diet (HFD) feeding and control groups. We measured glucose transport, mitochondrial respiration, UPRmt and histone methylation modification of UPRmt-related proteins to examine the UPRmt in the slow fiber-enriched soleus (Sol) and fast fiber-enriched tibialis anterior (TA) under HFD conditions.ResultsOur results indicate that 18 weeks of HFD can cause systemic IR, while the disturbance of Glut4-dependent glucose transport only occurred in fast-twitch muscle. The expression levels of UPRmt markers, including ATF5, HSP60 and ClpP, and the UPRmt-related mitokine MOTS-c were significantly higher in slow-twitch muscle than in fast-twitch muscle under HFD conditions. Mitochondrial respiratory function is maintained only in slow-twitch muscle. Additionally, in the Sol, histone methylation at the ATF5 promoter region was significantly higher than that in the TA after HFD feeding.ConclusionThe expression of proteins involved in glucose transport in slow-twitch muscle remains almost unaltered after HFD intervention, whereas a significant decline of these proteins was observed in fast-twitch muscle. Specific activation of the UPRmt in slow-twitch muscle, accompanied by higher mitochondrial respiratory function and MOTS-c expression, may contribute to the higher resistance to HFD in slow-twitch muscle. Notably, the different histone modifications of UPRmt regulators may underlie the specific activation of the UPRmt in different muscle types. However, future work applying genetic or pharmacological approaches should further uncover the relationship between the UPRmt and insulin resistance.

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The importance of mitochondrial quality control for maintaining skeletal muscle function across health span

Cited by 25 publications

References 76 publications

MicroRNAs as the Sentinels of Redox and Hypertrophic Signalling

MicroRNAs as the Sentinels of Redox and Hypertrophic Signalling

Reshaped Gut Microbial Composition and Functions Associated with the Antifatigue Effect of Salidroside in Exercise Mice

The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats

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