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Mitochondrial quality control mechanisms as potential therapeutic targets in sepsis-induced multiple organ failure

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Abstract

Sepsis is a dysregulated response to severe infection characterized by life-threatening organ failure and is the leading cause of mortality worldwide. Multiple organ failure is the central characteristic of sepsis and is associated with poor outcome of septic patients. Ultrastructural damage to the mitochondria and mitochondrial dysfunction are reported in sepsis. Mitochondrial dysfunction with subsequent ATP deficiency, excessive reactive oxygen species (ROS) release, and cytochrome c release are all considered to contribute to organ failure. Consistent mitochondrial dysfunction leads to reduced mitochondrial quality control capacity, which eliminates dysfunctional and superfluous mitochondria to maintain mitochondrial homeostasis. Mitochondrial quality is controlled through a series of processes including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, and transport processes. Several studies have indicated that multiple organ failure is ameliorated by restoring mitochondrial quality control mechanisms and is further amplified by defective quality control mechanisms. This review will focus on advances concerning potential mechanisms in regulating mitochondrial quality control and impacts of mitochondrial quality control on the progression of sepsis.

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Funding

This work was supported, in part, by grants from the National Natural Science Foundation (grant numbers 81571937 and 81772112).

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Authors and Affiliations

  1. Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China

    You Wu, Yong-Ming Yao & Zhong-Qiu Lu

  2. Wenzhou Municipal Key Laboratory of Emergency, Critical Care and Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China

    You Wu & Zhong-Qiu Lu

  3. Trauma Research Center, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing, People’s Republic of China

    Yong-Ming Yao

  4. College of Nursing, Wenzhou Medical University, Wenzhou, People’s Republic of China

    Zhong-Qiu Lu

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  1. You Wu
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Wu, Y., Yao, YM. & Lu, ZQ. Mitochondrial quality control mechanisms as potential therapeutic targets in sepsis-induced multiple organ failure. J Mol Med 97, 451–462 (2019). https://doi.org/10.1007/s00109-019-01756-2

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