New Insights into Targeting Mitochondria in Ischemic Injury

Overview

Journal Apoptosis

Publisher Springer

Date 2021 Mar 22

PMID 33751318

Citations 23

Authors

Jingjing Jia

Haiqiang Jin

Ding Nan

Weiwei Yu

Yining Huang

Affiliations

Soon will be listed here.

Abstract

Stroke is the leading cause of adult disability and death worldwide. Mitochondrial dysfunction has been recognized as a marker of neuronal death during ischemic stroke. Maintaining the function of mitochondria is important for improving the survival of neurons and maintaining neuronal function. Damaged mitochondria induce neuronal cell apoptosis by releasing reactive oxygen species (ROS) and pro-apoptotic factors. Mitochondrial fission and fusion processes and mitophagy are of great importance to mitochondrial quality control. This paper reviews the dynamic changes in mitochondria, the roles of mitochondria in different cell types, and related signaling pathways in ischemic stroke. This review describes in detail the role of mitochondria in the process of neuronal injury and protection in cerebral ischemia, and integrates neuroprotective drugs targeting mitochondria in recent years, which may provide a theoretical basis for the progress of treatment of ischemic stroke. The potential of mitochondrial-targeted therapy is also emphasized, which provides valuable insights for clinical research.

Citing Articles

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References

Adibhatla R, Hatcher J . Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies. CNS Neurol Disord Drug Targets. 2008; 7(3):243-53. PMC: 2562687. DOI: 10.2174/187152708784936608. View

Henninger N, Fisher M . Extending the Time Window for Endovascular and Pharmacological Reperfusion. Transl Stroke Res. 2016; 7(4):284-93. DOI: 10.1007/s12975-015-0444-4. View

Wang X, Asahi M, Lo E . Tissue type plasminogen activator amplifies hemoglobin-induced neurotoxicity in rat neuronal cultures. Neurosci Lett. 1999; 274(2):79-82. DOI: 10.1016/s0304-3940(99)00682-5. View

Segura T, Calleja S, Jordan J . Recommendations and treatment strategies for the management of acute ischemic stroke. Expert Opin Pharmacother. 2008; 9(7):1071-85. DOI: 10.1517/14656566.9.7.1071. View

Andrabi S, Parvez S, Tabassum H . Ischemic stroke and mitochondria: mechanisms and targets. Protoplasma. 2019; 257(2):335-343. DOI: 10.1007/s00709-019-01439-2. View

Yue R, Xia X, Jiang J, Yang D, Han Y, Chen X . Mitochondrial DNA oxidative damage contributes to cardiomyocyte ischemia/reperfusion-injury in rats: cardioprotective role of lycopene. J Cell Physiol. 2015; 230(9):2128-41. DOI: 10.1002/jcp.24941. View

Crack P, Taylor J . Reactive oxygen species and the modulation of stroke. Free Radic Biol Med. 2005; 38(11):1433-44. DOI: 10.1016/j.freeradbiomed.2005.01.019. View

Muller F, Liu Y, Van Remmen H . Complex III releases superoxide to both sides of the inner mitochondrial membrane. J Biol Chem. 2004; 279(47):49064-73. DOI: 10.1074/jbc.M407715200. View

Murphy M . How mitochondria produce reactive oxygen species. Biochem J. 2008; 417(1):1-13. PMC: 2605959. DOI: 10.1042/BJ20081386. View

10.

Lemasters J, Theruvath T, Zhong Z, Nieminen A . Mitochondrial calcium and the permeability transition in cell death. Biochim Biophys Acta. 2009; 1787(11):1395-401. PMC: 2730424. DOI: 10.1016/j.bbabio.2009.06.009. View

11.

Hamanaka R, Chandel N . Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes. Trends Biochem Sci. 2010; 35(9):505-13. PMC: 2933303. DOI: 10.1016/j.tibs.2010.04.002. View

12.

Nogueira V, Park Y, Chen C, Xu P, Chen M, Tonic I . Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis. Cancer Cell. 2008; 14(6):458-70. PMC: 3038665. DOI: 10.1016/j.ccr.2008.11.003. View

13.

Yang Y, Song Y, Loscalzo J . Regulation of the protein disulfide proteome by mitochondria in mammalian cells. Proc Natl Acad Sci U S A. 2007; 104(26):10813-7. PMC: 1904139. DOI: 10.1073/pnas.0702027104. View

14.

Kwon J, Lee S, Yang K, Ahn Y, Kim Y, Stadtman E . Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors. Proc Natl Acad Sci U S A. 2004; 101(47):16419-24. PMC: 534546. DOI: 10.1073/pnas.0407396101. View

15.

Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M . Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 2005; 120(5):649-61. DOI: 10.1016/j.cell.2004.12.041. View

16.

Sibson N, Dhankhar A, MASON G, Rothman D, Behar K, Shulman R . Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci U S A. 1998; 95(1):316-21. PMC: 18211. DOI: 10.1073/pnas.95.1.316. View

17.

Waagepetersen H, Sonnewald U, Gegelashvili G, Larsson O, Schousboe A . Metabolic distinction between vesicular and cytosolic GABA in cultured GABAergic neurons using 13C magnetic resonance spectroscopy. J Neurosci Res. 2001; 63(4):347-55. DOI: 10.1002/1097-4547(20010215)63:4<347::AID-JNR1029>3.0.CO;2-G. View

18.

Cheng A, Hou Y, Mattson M . Mitochondria and neuroplasticity. ASN Neuro. 2010; 2(5):e00045. PMC: 2949087. DOI: 10.1042/AN20100019. View

19.

Bakthavachalam P, Shanmugam P . Mitochondrial dysfunction - Silent killer in cerebral ischemia. J Neurol Sci. 2017; 375:417-423. DOI: 10.1016/j.jns.2017.02.043. View

20.

Valko M, Leibfritz D, Moncol J, Cronin M, Mazur M, Telser J . Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2006; 39(1):44-84. DOI: 10.1016/j.biocel.2006.07.001. View