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Review
. 2024 Dec;46(2):2393262.
doi: 10.1080/0886022X.2024.2393262. Epub 2024 Aug 27.

Mitochondrial dysfunction in acute kidney injury

Congcong Yao  1 , Ziwei Li  1 , Keke Sun  1 , Yan Zhang  1 , Songtao Shou  1 , Heng Jin  1
Affiliations
Review

Mitochondrial dysfunction in acute kidney injury

Congcong Yao et al. Ren Fail. 2024 Dec.

Abstract

Acute kidney injury (AKI) is a systemic clinical syndrome increasing morbidity and mortality worldwide in recent years. Renal tubular epithelial cells (TECs) death caused by mitochondrial dysfunction is one of the pathogeneses. The imbalance of mitochondrial quality control is the main cause of mitochondrial dysfunction. Mitochondrial quality control plays a crucial role in AKI. Mitochondrial quality control mechanisms are involved in regulating mitochondrial integrity and function, including antioxidant defense, mitochondrial quality control, mitochondrial DNA (mtDNA) repair, mitochondrial dynamics, mitophagy, and mitochondrial biogenesis. Currently, many studies have used mitochondrial dysfunction as a targeted therapeutic strategy for AKI. Therefore, this review aims to present the latest research advancements on mitochondrial dysfunction in AKI, providing a valuable reference and theoretical foundation for clinical prevention and treatment of this condition, ultimately enhancing patient prognosis.

Keywords: Acute kidney injury; mitochondrial biogenesis; mitochondrial dynamics; mitochondrial quality control; mitophagy.

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Conflict of interest statement

The authors declare no conflicts of interest. The figures in the manuscript were drawn in Figdraw.

Figures

Figure 1.
Figure 1.
Mitochondrial dysfunction in AKI. After the kidney is damaged by various factors, under the involvement of a variety of mitochondrial quality control mechanisms, severe hypoxia, and acidosis of TECs lead to atrophy, necrosis, and apoptosis.
Figure 2.
Figure 2.
Mitochondrial quality control. Mitochondria quality control includes the biogenesis of mitochondrial structural proteins from nuclear DNA and dynamic remodeling of the mitochondrial network via fission and fusion to maintain an optimally functioning mass of mitochondria within the cell. PPAR-α: peroxisome proliferator-activated receptor alpha; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator-1 alpha; NRF1/2: nuclear respiratory factor 1/2; TFAM: mitochondrial transcription factor A; ERR1: estrogen-related receptor-1; OPA1: optic atrophy 1; MFN1/2: mitochondrial fusion protein 1/2; DRP1: dynamin-related protein-1; YY1: transcriptional repressor protein 1; ΔΨm: mitochondrial transmembrane potential; ROS, reactive oxygen species; OXPHOS: Oxidative phosphorylation.
Figure 3.
Figure 3.
Molecular mechanisms of mitophagy. There are two major mechanisms for mitochondrial priming in mitophagy. In the PINK1/PARK2 pathway, mitochondrial damage or depolarization impairs the import of PINK1 into the mitochondria, resulting in the accumulation of PINK1 on OMM. Then, PINK1 recruits PINK2 from the cytosol and activates its E3 ligase activity via phosphorylation. Upon activation, PINK2 catalyzes the formation of poly-ubiquitin chains on OMM proteins. In the mitophagy receptor pathway, BNIP3、BNIP3L/NIX and FUNDC1 mitophagy receptors localize to the OMM and interact directly with LC3 to mediate mitochondrial elimination.PINK1: PTEN-induced putative kinase-1; parkin: Parkinson protein-2 E3 ubiquitin protein ligase; BNIP3: BCL-2/adenovirus E1B 19 kDa protein-interacting protein 3; BNIP3L: BCL-2/adenovirus E1B 19 kDa protein-interacting protein 3-like; nix: NIP3-like protein X; FUNDC1: FUN14 domain-containing 1; IMM: inner mitochondrial membrane; OMM: outer mitochondrial membrane; LC3: light chain 3.
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References

    1. Pickkers P, Darmon M, Hoste E, et al. . Acute kidney injury in the critically ill: an updated review on pathophysiology and management. Intensive Care Med. 2021;47(8):835–850. doi: 10.1007/s00134-021-06454-7. - DOI - PMC - PubMed
    1. Mehta RL, Cerdá J, Burdmann EA, et al. . International Society of Nephrology’s 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology. Lancet. 2015;385(9987):2616–2643. doi: 10.1016/S0140-6736(15)60126-X. - DOI - PubMed
    1. Hoste EAJ, Kellum JA, Selby NM, et al. . Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol. 2018;14(10):607–625. doi: 10.1038/s41581-018-0052-0. - DOI - PubMed
    1. Noble RA, Lucas BJ, Selby NM.. Long-term outcomes in patients with acute kidney injury. Clin J Am Soc Nephrol. 2020;15(3):423–429. doi: 10.2215/CJN.10410919. - DOI - PMC - PubMed
    1. Sun K, Shi Z, Abudureheman Y, et al. . Clinical and epidemiological characteristics of rhabdomyolysis: a retrospective study. Int J Clin Pract. 2023;2023:6396576–6396511. doi: 10.1155/2023/6396576. - DOI - PMC - PubMed

Grants and funding

This research was funded by The National Natural Science Foundation of China [Grant Number: 82072222]; the Science and Technology Fund of Tianjin Municipal Education Commission [grant number: 2021KJ216].

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