Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondria
Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Skeletal muscle atrophy due to critical illness is a common phenomenon in the intensive care unit (ICU) and is referred to as ICU-acquired weakness (ICU-AW). The occurrence of ICU-AW in pat...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2025.1520669/full |
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| author | Luying Yang Leiyu Xie Min Li Yanmei Miao Jun Yang Shaolin Chen Xinglong Ma Peng Xie Peng Xie |
| author_facet | Luying Yang Leiyu Xie Min Li Yanmei Miao Jun Yang Shaolin Chen Xinglong Ma Peng Xie Peng Xie |
| author_sort | Luying Yang |
| collection | DOAJ |
| description | Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Skeletal muscle atrophy due to critical illness is a common phenomenon in the intensive care unit (ICU) and is referred to as ICU-acquired weakness (ICU-AW). The occurrence of ICU-AW in patients with sepsis is known as sepsis-acquired weakness (SAW). Furthermore, it is well known that maintaining normal muscle function closely relates to mitochondrial homeostasis. Once mitochondrial function is impaired, both muscle quality and function are affected. Copper plays a key role in mitochondrial homeostasis as a transition metal that regulates the function and stability of various enzymes. Copper is also involved in oxidation-reduction reactions, and intracellular copper overload causes oxidative stress and induces cell death. Previous studies have shown that excess intracellular copper induces cell death by targeting lipid-acylated proteins that regulate the mitochondrial tricarboxylic acid (TCA) cycle, which differs from the known canonical mechanisms of regulated cell death. Furthermore, inhibitors of cell death, such as apoptosis, necroptosis, pyroptosis and ferroptosis, are not effective in preventing copper-induced cell death. This new form of cell death has been termed “Cuproptosis”; however, the mechanism by which copper-induced cell death is involved in SAW remains unclear. In this paper, we review the possible relationship between cuproptosis and SAW. Cuproptosis may be involved in regulating the pathological mechanisms of SAW through mitochondria-related signaling pathways, mitochondria-related ferroptosis mechanisms, and mitochondria-related genes, and to provide new ideas for further investigations into the mechanism of SAW. |
| format | Article |
| id | doaj-art-c7f465728d544d2bbb45b32b66d7ab25 |
| institution | OA Journals |
| issn | 1664-042X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj-art-c7f465728d544d2bbb45b32b66d7ab252025-08-20T01:49:28ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-03-011610.3389/fphys.2025.15206691520669Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondriaLuying Yang0Leiyu Xie1Min Li2Yanmei Miao3Jun Yang4Shaolin Chen5Xinglong Ma6Peng Xie7Peng Xie8Department of Critical Care Medicine of the Third Affiliated Hospital (The First People’s Hospital of Zunyi), Zunyi Medical University, Zunyi, ChinaDepartment of Critical Care Medicine of the Third Affiliated Hospital (The First People’s Hospital of Zunyi), Zunyi Medical University, Zunyi, ChinaDepartment of Critical Care Medicine of the Third Affiliated Hospital (The First People’s Hospital of Zunyi), Zunyi Medical University, Zunyi, ChinaDepartment of Critical Care Medicine of the Third Affiliated Hospital (The First People’s Hospital of Zunyi), Zunyi Medical University, Zunyi, ChinaDepartment of Critical Care Medicine of the Third Affiliated Hospital (The First People’s Hospital of Zunyi), Zunyi Medical University, Zunyi, ChinaDepartment of Nursing of Affiliated Hospital, Zunyi Medical University, Zunyi, ChinaDepartment of Critical Care Medicine of the Third Affiliated Hospital (The First People’s Hospital of Zunyi), Zunyi Medical University, Zunyi, ChinaDepartment of Critical Care Medicine of the Third Affiliated Hospital (The First People’s Hospital of Zunyi), Zunyi Medical University, Zunyi, ChinaDepartment of Critical Care Medicine, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, ChinaSepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Skeletal muscle atrophy due to critical illness is a common phenomenon in the intensive care unit (ICU) and is referred to as ICU-acquired weakness (ICU-AW). The occurrence of ICU-AW in patients with sepsis is known as sepsis-acquired weakness (SAW). Furthermore, it is well known that maintaining normal muscle function closely relates to mitochondrial homeostasis. Once mitochondrial function is impaired, both muscle quality and function are affected. Copper plays a key role in mitochondrial homeostasis as a transition metal that regulates the function and stability of various enzymes. Copper is also involved in oxidation-reduction reactions, and intracellular copper overload causes oxidative stress and induces cell death. Previous studies have shown that excess intracellular copper induces cell death by targeting lipid-acylated proteins that regulate the mitochondrial tricarboxylic acid (TCA) cycle, which differs from the known canonical mechanisms of regulated cell death. Furthermore, inhibitors of cell death, such as apoptosis, necroptosis, pyroptosis and ferroptosis, are not effective in preventing copper-induced cell death. This new form of cell death has been termed “Cuproptosis”; however, the mechanism by which copper-induced cell death is involved in SAW remains unclear. In this paper, we review the possible relationship between cuproptosis and SAW. Cuproptosis may be involved in regulating the pathological mechanisms of SAW through mitochondria-related signaling pathways, mitochondria-related ferroptosis mechanisms, and mitochondria-related genes, and to provide new ideas for further investigations into the mechanism of SAW.https://www.frontiersin.org/articles/10.3389/fphys.2025.1520669/fullsepsis-acquired weaknesscuproptosismitochondriacoppercell death |
| spellingShingle | Luying Yang Leiyu Xie Min Li Yanmei Miao Jun Yang Shaolin Chen Xinglong Ma Peng Xie Peng Xie Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondria Frontiers in Physiology sepsis-acquired weakness cuproptosis mitochondria copper cell death |
| title | Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondria |
| title_full | Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondria |
| title_fullStr | Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondria |
| title_full_unstemmed | Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondria |
| title_short | Potential relationship between cuproptosis and sepsis-acquired weakness: an intermediate role for mitochondria |
| title_sort | potential relationship between cuproptosis and sepsis acquired weakness an intermediate role for mitochondria |
| topic | sepsis-acquired weakness cuproptosis mitochondria copper cell death |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2025.1520669/full |
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