Restoring the infected powerhouse: Mitochondrial quality control in sepsis

Lira Chavez, F.M.; Gartzke, L.P.; van Beuningen, F.E.; Wink, S.E.; Henning, R.H.; Krenning, G.; Bouma, H.R.

doi:10.1016/j.redox.2023.102968

Cited by 8 publications

(1 citation statement)

References 184 publications

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“…4B, C]. To further evaluate CLP-induced mitochondrial damage and the protective effects of NSA or Mdivi-1, cellular ROS levels, indicative of mitochondrial damage, were measured [7,40]. The results showed that sepsis-induced increases in ROS levels were repressed by the administration of NSA or Mdivi-1 [F (3, 14) = 5.199, P = 0.0127, Fig.…”

Section: Inhibiting Gsdmd or Drp1 Protected Against Mitochondrial And...mentioning

confidence: 99%

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy

Fu,

Zhang,

Shi

et al. 2024

J Neuroinflammation

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Background Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. Methods C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. Results CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. Conclusions Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

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Section: Inhibiting Gsdmd or Drp1 Protected Against Mitochondrial And...mentioning

confidence: 99%

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy

Fu,

Zhang,

Shi

et al. 2024

J Neuroinflammation

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The emerging role of mtDNA release in sepsis: Current evidence and potential therapeutic targets

Hong,

Zhu,

et al. 2024

Journal Cellular Physiology

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Sepsis is a systemic inflammatory reaction caused by infection, and severe sepsis can develop into septic shock, eventually leading to multiorgan dysfunction and even death. In recent years, studies have shown that mitochondrial damage is closely related to the occurrence and development of sepsis. Recent years have seen a surge in concern over mitochondrial DNA (mtDNA), as anomalies in this material can lead to cellular dysfunction, disruption of aerobic respiration, and even death of the cell. In this review, we discuss the latest findings on the mechanisms of mitochondrial damage and the molecular mechanisms controlling mitochondrial mtDNA release. We also explored the connection between mtDNA misplacement and inflammatory activation. Additionally, we propose potential therapeutic targets of mtDNA for sepsis treatment.

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“Mitolocalization”

Kraft

2024

CHEST Critical Care

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Restoring the infected powerhouse: Mitochondrial quality control in sepsis

Cited by 8 publications

References 184 publications

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy

The emerging role of mtDNA release in sepsis: Current evidence and potential therapeutic targets

“Mitolocalization”

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