Regulation of Oxidative Phosphorylation of Liver Mitochondria in Sepsis

Eyenga, Pierre; Rey, Benjamin; Eyenga, Lilia; Sheu, Shey Shing

doi:10.3390/cells11101598

Cited by 11 publications

(9 citation statements)

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“…Thus, whenever considering the energy demands of the muscles, it is mandatory to take account of the mitochondrial function of hepatocytes and—for the effort of transporting oxygen and metabolites—cardiomyocytes. In both organs, severe alterations occur during sepsis [ 19 , 20 ].…”

Section: Mitochondrial Structure and Function In Healthy Skeletal Musclementioning

confidence: 99%

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: Mitochondrial Structure and Function In Healthy Skeletal Musclementioning

confidence: 99%

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 the main utilisers of oxygen and producers of reactive oxygen species (ROS) within the body, and their activity and turnover (biogenesis) are influenced by multiple hormones. Mitochondrial dysfunction is well described in sepsis [ 11 ] and is implicated in failure affecting multiple organs including heart [ 12 ], kidney [ 13 ], liver [ 14 ] and brain [ 15 ]. The role in immune dysfunction is discussed below.…”

Section: Sepsis – Definitions Clinical Features and Pathophysiologymentioning

confidence: 99%

The role of hormones in sepsis: an integrated overview with a focus on mitochondrial and immune cell dysfunction

et al. 2023

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Sepsis is a dysregulated host response to infection that results in life-threatening organ dysfunction. Virtually every body system can be affected by this syndrome to greater or lesser extents. Gene transcription and downstream pathways are either up- or downregulated, albeit with considerable fluctuation over the course of the patient’s illness. This multi-system complexity contributes to a pathophysiology that remains to be fully elucidated. Consequentially, little progress has been made to date in developing new outcome-improving therapeutics. Endocrine alterations are well characterised in sepsis with variations in circulating blood levels and/or receptor resistance. However, little attention has been paid to an integrated view of how these hormonal changes impact upon the development of organ dysfunction and recovery. Here, we present a narrative review describing the impact of the altered endocrine system on mitochondrial dysfunction and immune suppression, two interlinked and key aspects of sepsis pathophysiology.

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“…O aumento da expressão e atividade dessas proteínas poderia explicar o aumento na respiração em Estado 4 sem fosforilação observado durante a sepse. A regulação positiva da síntese de mRNA da UCP-2 é acompanhada por uma redução na geração de ROS nas mitocôndrias hepáticas de ratos com sepse, mas não afeta o vazamento de prótons (Eyenga et al, 2022).…”

Section: Discussionunclassified

“…Pode-se dizer que a respiração celular é reduzida em hepatócitos, com disfunção do Complexo respiratório II, succinato desidrogenase, em células isoladas durante a sepse. Eyenga et al (2022), utilizando ligadura e punção cecal (CLP), demonstrou um aumento no consumo de oxigênio de mitocôndrias hepáticas isoladas. Esses resultados foram surpreendentes, considerando que o consumo de oxigênio de hepatócitos foi constatado como reduzido durante a sepse segundo Kantrow et al (1997).…”

Section: Discussionunclassified

“…Em homeostase, a eficiência da fosforilação oxidativa é definida de modo que o acoplamento entre a oxidação de substratos (respiração mitocondrial) e a produção de ATP possa atender à demanda celular de ATP. Em contrapartida, quando o estímulo da oxidação de substratos (consumo de oxigênio mitocondrial) não leva a um aumento na geração de ATP em proporção estequiométrica, isso expressa um desacoplamento das reações de oxidação e fosforilação (Eyenga et al, 2022).…”

Section: Fosforilação Oxidativaunclassified

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Efeito da tolerância ao Lipopolissacarídeo (LPS) no desacoplamento mitocondrial da sepse

Silvestre¹

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Sepsis has organic dysfunctions due to a dysregulated inflammatory response that alters cellular functions. This cell damage occurs with significant changes to metabolic pathways and to cellular function. Uncoupling proteins (UCPs) are located in the inner mitochondrial membrane, playing roles that include heat production and regulation of the production of reactive oxygen species by mitochondria. Mitochondrial respiration results in proton extrusion (H+) outside the mitochondria and inside the intermembrane space, establishing the mitochondrial membrane potential. UCPs pump protons from the intermembrane space to the mitochondrial matrix and, thus, dissipate the proton gradient, reduce ATP production, and decrease superoxide production. Hence, UCPs play important roles in redox regulation and in mitochondrial and metabolic processes. This study has the purpose of evaluating the effects of LPS tolerance in mitochondrial uncoupling in an experimental model of sepsis, in addition to evaluating mitochondrial damage through the amount of mitochondria present in liver tissue and investigating oxygen consumption in mitochondria isolated from the liver tissue. Male, 7week-old, Balb/c mice were used, which underwent sepsis stimulation through cecal ligation and puncture (CLP) technique and induction of Escherichia coli lipopolysaccharide (LPS) tolerance. The animals were euthanized 24 hours after CLP procedure and the material was collected. The results found in this study show increased levels of UCP-1 in both groups undergoing CLP procedure, and tolerance did not change animal response. On the other hand, a reduction was seen in UCP-2 and UCP-3 levels both in the liver and in the heart of animals undergoing CLP procedure when compared to Control and Tolerant groups, also with no influence of tolerance on these UCPs. The quantification of mitochondrial DNA showed that there were no statistical differences when comparing the groups under analysis. Data showed a reduction in oxygen consumption in CLP group in State 2 when compared to Control and Tolerant groups, as well as a reduction in oxygen consumption in CLPT group in State 2 when compared to the Tolerant group, showing a deficit in oxidative metabolism in septic animals. Future studies with other periods may elucidate the metabolism cycle of UCPs in tolerance and in sepsis.

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Regulation of Oxidative Phosphorylation of Liver Mitochondria in Sepsis

Cited by 11 publications

References 85 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

The role of hormones in sepsis: an integrated overview with a focus on mitochondrial and immune cell dysfunction

Efeito da tolerância ao Lipopolissacarídeo (LPS) no desacoplamento mitocondrial da sepse

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