Sepsis Disrupts Mitochondrial Function and Diaphragm Morphology

Oliveira, Thamires Siqueira; Santos, Anderson Teixeira; Andrade, Cherley Borba Vieira de; Silva, Johnatas D.; Blánco, N.; Rocha, Nazareth de Novaes; Woyames, Juliana; Silva, Pedro L.; Rocco, Patrícia Rieken Macêdo; da‐Silva, Wagner Seixas; Ortiga-Carvalho, Tânia M.; Bloise, Flávia Fonseca

doi:10.3389/fphys.2021.704044

Cited by 13 publications

(12 citation statements)

References 43 publications

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“…In an animal model of severe burn injury (with full-thickness burns, 60% of the total body surface area), a 36% decrease in the number of mitochondria was observed [ 101 ]. Similar results have been demonstrated in septic mice; a loss of about 30% was seen in limb and respiratory skeletal muscles [ 102 ]. This results are in line with data from critically ill patients with sepsis and MOF, in whom overall mitochondrial degradation was evident [ 13 ].…”

Section: Structural and Functional Impairments Of Mitochondria In Icu...supporting

confidence: 87%

“…Pharmacologically-induced activation of NRF2 has been evaluated in an attempt to promote mitochondrial biogenesis and, therefore, to restore mitochondrial count, with positive results [ 213 , 214 ]. This seems conclusive, since a reduction in the mitochondrial content of the overall skeletal muscles is frequently observed in critical illness [ 101 , 102 ]. Beyond activation of biogenesis, inhibition of overshooting mitochondrial fission might also provide interesting attempts to overcome mitochondrial dysfunction.…”

Section: Dynamics Of Mitochondrial Alterations and Therapeutic Implic...mentioning

confidence: 95%

“…However, the results were expressed as activity per gram protein, making conclusions in regard to the function status of the ETC enzymes difficult. In another investigation, Oliveira and coworkers reported a marked downregulation of all ETC enzyme complex mRNAs, as well as a reduced protein expression of the complexes III and IV in the diaphragms of septic mice [ 102 ]. Skeletal muscles of not only the respiratory system, but also of the limbs, experience significant alterations in their OXPHOS systems.…”

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

“…Furthermore, not only an overproduction of ROS, but also a downregulation of antioxidant systems seems to be at hand in critical illness [ 81 , 115 ]. In skeletal muscles, the combined effect of muscle unloading and systemic inflammation could further augment oxidative stress and downregulate antioxidant defense mechanisms such as SOD 2 [ 102 ]. Besides the direct downregulation of gene expression, the inability to translocate nuclear transcription factors that are essential for mitochondrial protein synthesis could also be hypothesized as a potential mechanism in antioxidant response failure [ 108 ].…”

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

“…This was also recently confirmed in patients with CIM [ 77 ]. Especially genes for mitochondrial fusion and replication, such as PGC1α, MFN2 and OPA1, seem to be affected in skeletal muscles [ 102 , 114 ]. Therefore, PGC1α mRNA expression is already significantly downregulated in skeletal muscles within the first days after ICU admission, indicating impairments in mitochondrial biogenesis and turnover in the early phase of critical illness [ 78 , 90 ].…”

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

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Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

Klawitter

Ehler

Bajorat

et al. 2023

IJMS

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Mitochondria are key structures providing most of the energy needed to maintain homeostasis. They are the main source of adenosine triphosphate (ATP), participate in glucose, lipid and amino acid metabolism, store calcium and are integral components in various intracellular signaling cascades. However, due to their crucial role in cellular integrity, mitochondrial damage and dysregulation in the context of critical illness can severely impair organ function, leading to energetic crisis and organ failure. Skeletal muscle tissue is rich in mitochondria and, therefore, particularly vulnerable to mitochondrial dysfunction. Intensive care unit-acquired weakness (ICUAW) and critical illness myopathy (CIM) are phenomena of generalized weakness and atrophying skeletal muscle wasting, including preferential myosin breakdown in critical illness, which has also been linked to mitochondrial failure. Hence, imbalanced mitochondrial dynamics, dysregulation of the respiratory chain complexes, alterations in gene expression, disturbed signal transduction as well as impaired nutrient utilization have been proposed as underlying mechanisms. This narrative review aims to highlight the current known molecular mechanisms immanent in mitochondrial dysfunction of patients suffering from ICUAW and CIM, as well as to discuss possible implications for muscle phenotype, function and therapeutic approaches.

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Section: Structural and Functional Impairments Of Mitochondria In Icu...supporting

confidence: 87%

Section: Dynamics Of Mitochondrial Alterations and Therapeutic Implic...mentioning

confidence: 95%

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

Section: Structural and Functional Impairments Of Mitochondria In Icu...mentioning

confidence: 99%

See 3 more Smart Citations

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

Klawitter

Ehler

Bajorat

et al. 2023

IJMS

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Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantation

Xiao,

Feng,

Jia

et al. 2023

J cachexia sarcopenia muscle

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BackgroundSepsis‐associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis‐induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis‐associated muscle weakness.MethodsIn a lipopolysaccharide (LPS)‐induced inflammation mouse model, mice with different sensitivities to LPS‐induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS‐triggered muscle damage was investigated, and the underlying mechanism was explored.ResultsRecipients exhibited varying LPS‐triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF‐1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO‐1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy‐related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF‐κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels.ConclusionsVitamin K1 might ameliorate LPS‐triggered skeletal muscle damage by antagonizing NF‐κB‐mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.

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β-hydroxybutyrate exposure restores mitochondrial function in skeletal muscle satellite cells of critically ill patients

Genserová,

Duška,

Krajčová

2024

Clinical Nutrition

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Sepsis Disrupts Mitochondrial Function and Diaphragm Morphology

Cited by 13 publications

References 43 publications

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

Mitochondrial Dysfunction in Intensive Care Unit-Acquired Weakness and Critical Illness Myopathy: A Narrative Review

Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantation

β-hydroxybutyrate exposure restores mitochondrial function in skeletal muscle satellite cells of critically ill patients

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