线粒体功能障碍引起的相关炎性疾病及靶向治疗

doi:10.13560/j.cnki.biotech.bull.1985.2022-1146

摘要/Abstract

摘要：

作为真核细胞中必不可少的细胞器，线粒体在能量代谢、维持氧化还原平衡和细胞凋亡调节中起着核心作用。线粒体功能障碍无论是由于线粒体自身受损、线粒体DNA基因突变或者是有缺陷的线粒体电子传递链、氧化应激，还是异常基因和炎性信号传导引起，都会对组织或器官造成一定的损伤或导致炎症的发生，如肾脏、肝脏、乳腺等器官或组织。本文总结了线粒体中重要组分包括线粒体DNA、细胞色素c和心磷脂的功能，及线粒体功能障碍引起的炎症疾病以及对线粒体功能障碍的治疗，以期为线粒体功能障碍与炎症疾病及靶向治疗提供更多技术支撑。

关键词: 线粒体功能障碍, 炎性疾病

Abstract:

As an essential organelle in eukaryotic cells, mitochondria play a central role in energy metabolism, maintenance of redox balance and regulation of apoptosis. Mitochondrial dysfunction, whether caused by mitochondrial damage, mitochondrial DNA gene mutation or defective mitochondrial electron transport chain, oxidative stress, or abnormal genes and inflammatory signal transduction, will cause certain damages to tissues or organs or lead to inflammation, such as kidney, liver, breast and other organs or tissues. This paper summarized the functions of important components in mitochondria, including mitochondrial DNA, cytochrome c and cardiolipin, and the inflammatory diseases caused by mitochondrial dysfunction, as well as the treatment of mitochondrial dysfunction, aiming to provide more technical support for mitochondrial dysfunction, inflammatory diseases and targeted therapy.

Key words: mitochondrial dysfunction, inflammatory diseases

马学虎, 马莉花, 苟妍, 马燕芬. 线粒体功能障碍引起的相关炎性疾病及靶向治疗[J]. 生物技术通报, 2023, 39(6): 119-125.

MA Xue-hu, MA Li-hua, GOU Yan, MA Yan-fen. Related Inflammatory Diseases Caused by Mitochondrial Dysfunction and Targeted Therapy to Them[J]. Biotechnology Bulletin, 2023, 39(6): 119-125.

参考文献 52

[7]	Tang BM, Huang SJ, McLean AS. Genome-wide transcription profiling of human sepsis: a systematic review[J]. Crit Care, 2010, 14(6): R237. doi: 10.1186/cc9392 URL
[8]	Wellington M, Koselny K, Sutterwala FS, et al. Candida albicans triggers NLRP3-mediated pyroptosis in macrophages[J]. Eukaryot Cell, 2014, 13(2): 329-340. doi: 10.1128/EC.00336-13 pmid: 24376002
[9]	Gurung P, Lukens JR, Kanneganti TD. Mitochondria: diversity in the regulation of the NLRP3 inflammasome[J]. Trends Mol Med, 2015, 21(3): 193-201. doi: 10.1016/j.molmed.2014.11.008 pmid: 25500014
[10]	Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes[J]. Cell, 2014, 157(5): 1013-1022. doi: 10.1016/j.cell.2014.04.007 pmid: 24855941
[11]	Kukat C, Davies KM, Wurm CA, et al. Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid[J]. Proc Natl Acad Sci USA, 2015, 112(36): 11288-11293. doi: 10.1073/pnas.1512131112 pmid: 26305956
[12]	Qi Y, Ye YD, Wang RX, et al. Mitochondrial dysfunction by TFAM depletion disrupts self-renewal and lineage differentiation of human PSCs by affecting cell proliferation and YAP response[J]. Redox Biol, 2022, 50: 102248. doi: 10.1016/j.redox.2022.102248 URL
[13]	Zhao M, Wang YZ, Li L, et al. Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance[J]. Theranostics, 2021, 11(4): 1845-1863. doi: 10.7150/thno.50905 pmid: 33408785
[14]	Alvarez-Paggi D, Hannibal L, Castro MA, et al. Multifunctional cytochrome c: learning new tricks from an old dog[J]. Chem Rev, 2017, 117(21): 13382-13460. doi: 10.1021/acs.chemrev.7b00257 pmid: 29027792
[15]	Rajagopal BS, Edzuma AN, Hough MA, et al. The hydrogen-peroxide-induced radical behaviour in human cytochrome c-phospholipid complexes: implications for the enhanced pro-apoptotic activity of the G41S mutant[J]. Biochem J, 2013, 456(3): 441-452. doi: 10.1042/BJ20130758 pmid: 24099549
[16]	Wang ZB, Li M, Zhao YG, et al. Cytochrome C is a hydrogen peroxide scavenger in mitochondria[J]. Protein Pept Lett, 2003, 10(3): 247-253. doi: 10.2174/0929866033479013 URL
[17]	Schlame M, Haldar D. Cardiolipin is synthesized on the matrix side of the inner membrane in rat liver mitochondria[J]. J Biol Chem, 1993, 268(1): 74-79. pmid: 8380172
[18]	Tuller G, Nemec T, Hrastnik C, et al. Lipid composition of subcellular membranes of an FY1679-derived haploid yeast wild-type strain grown on different carbon sources[J]. Yeast, 1999, 15(14): 1555-1564. pmid: 10514572
[19]	Chu CT, Bayır H, Kagan VE. LC3 binds externalized cardiolipin on injured mitochondria to signal mitophagy in neurons: implications for Parkinson disease[J]. Autophagy, 2014, 10(2): 376-378. doi: 10.4161/auto.27191 pmid: 24351649
[20]	Kagan VE, Tyurin VA, Jiang JF, et al. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors[J]. Nat Chem Biol, 2005, 1(4): 223-232. pmid: 16408039
[21]	Chao HL, Anthonymuthu TS, Kenny EM, et al. Disentangling oxidation/hydrolysis reactions of brain mitochondrial cardiolipins in pathogenesis of traumatic injury[J]. JCI Insight, 2018, 3(21): e97677. doi: 10.1172/jci.insight.97677 URL
[22]	Phan K, He Y, Pickford R, et al. Uncovering pathophysiological changes in frontotemporal dementia using serum lipids[J]. Sci Rep, 2020, 10(1): 3640. doi: 10.1038/s41598-020-60457-w pmid: 32107421
[23]	Dudek J. Role of cardiolipin in mitochondrial signaling pathways[J]. Front Cell Dev Biol, 2017, 5: 90. doi: 10.3389/fcell.2017.00090 pmid: 29034233
[24]	Musatov A, Sedlák E. Role of cardiolipin in stability of integral membrane proteins[J]. Biochimie, 2017, 142: 102-111. doi: S0300-9084(17)30222-5 pmid: 28842204
[25]	Duncan AL, Robinson AJ, Walker JE. Cardiolipin binds selectively but transiently to conserved lysine residues in the rotor of metazoan ATP synthases[J]. Proc Natl Acad Sci USA, 2016, 113(31): 8687-8692. doi: 10.1073/pnas.1608396113 pmid: 27382158
[26]	Garcia-Martinez I, Santoro N, Chen YL, et al. Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9[J]. J Clin Invest, 2016, 126(3): 859-864. doi: 10.1172/JCI83885 pmid: 26808498
[27]	Hao LY, Zhong W, Dong HB, et al. ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1-TFAM signalling in alcoholic steatohepatitis[J]. Gut, 2021, 70(10): 1933-1945. doi: 10.1136/gutjnl-2020-321548 URL
[28]	Hu K, Xiao LD, Li LJ, et al. The mitochondria-targeting antioxidant MitoQ alleviated lipopolysaccharide/d-galactosamine-induced acute liver injury in mice[J]. Immunol Lett, 2021, 240: 24-30. doi: 10.1016/j.imlet.2021.09.003 URL
[29]	Menezes-Filho SL, Amigo I, Luévano-Martínez LA, et al. Fasting promotes functional changes in liver mitochondria[J]. Biochim Biophys Acta Bioenerg, 2019, 1860(2): 129-135. doi: 10.1016/j.bbabio.2018.11.017 URL
[30]	Ipsen DH, Lykkesfeldt J, Tveden-Nyborg P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease[J]. Cell Mol Life Sci, 2018, 75(18): 3313-3327. doi: 10.1007/s00018-018-2860-6 pmid: 29936596
[31]	Li XY, Zhang W, Cao QT, et al. Mitochondrial dysfunction in fibrotic diseases[J]. Cell Death Discov, 2020, 6: 80. doi: 10.1038/s41420-020-00316-9 pmid: 32963808
[32]	Ratliff BB, Abdulmahdi W, Pawar R, et al. Oxidant mechanisms in renal injury and disease[J]. Antioxid Redox Signal, 2016, 25(3): 119-146. doi: 10.1089/ars.2016.6665 URL
[33]	Zhang XQ, Agborbesong E, Li XG. The role of mitochondria in acute kidney injury and chronic kidney disease and its therapeutic potential[J]. Int J Mol Sci, 2021, 22(20): 11253. doi: 10.3390/ijms222011253 URL
[34]	Kang I, Chu CT, Kaufman BA. The mitochondrial transcription factor TFAM in neurodegeneration: emerging evidence and mechanisms[J]. FEBS Lett, 2018, 592(5): 793-811. doi: 10.1002/1873-3468.12989 pmid: 29364506
[35]	Duann P, Lin PH. Mitochondria damage and kidney disease[J]. Adv Exp Med Biol, 2017, 982: 529-551. doi: 10.1007/978-3-319-55330-6_27 pmid: 28551805
[36]	Smith JA, Stallons LJ, Collier JB, et al. Suppression of mitochondrial biogenesis through toll-like receptor 4-dependent mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling in endotoxin-induced acute kidney injury[J]. J Pharmacol Exp Ther, 2015, 352(2): 346-357. doi: 10.1124/jpet.114.221085 pmid: 25503387
[1]	Gómez-Crisóstomo NP, López-Marure R, Zapata E, et al. Bax induces cytochrome c release by multiple mechanisms in mitochondria from MCF7 cells[J]. J Bioenerg Biomembr, 2013, 45(5): 441-448. doi: 10.1007/s10863-013-9508-x pmid: 23536162
[2]	Zhang K, Zhou XT, Wang JQ, et al. Dendrobium officinale polysaccharide triggers mitochondrial disorder to induce colon cancer cell death via ROS-AMPK-autophagy pathway[J]. Carbohydr Polym, 2021, 264: 118018. doi: 10.1016/j.carbpol.2021.118018 URL
[3]	Becker T, Guiard B, Thornton N, et al. Assembly of the mitochondrial protein import channel: role of Tom5 in two-stage interaction of Tom40 with the SAM complex[J]. Mol Biol Cell, 2010, 21(18): 3106-3113. doi: 10.1091/mbc.E10-06-0518 pmid: 20668160
[4]	Rizwan H, Pal S, Sabnam S, et al. High glucose augments ROS generation regulates mitochondrial dysfunction and apoptosis via stress signalling cascades in keratinocytes[J]. Life Sci, 2020, 241: 117148. doi: 10.1016/j.lfs.2019.117148 URL
[5]	Chuang KC, Chang CR, Chang SH, et al. Imiquimod-induced ROS production disrupts the balance of mitochondrial dynamics and increases mitophagy in skin cancer cells[J]. J Dermatol Sci, 2020, 98(3): 152-162. doi: 10.1016/j.jdermsci.2020.03.009 URL
[6]	Ke HZ, Lee S, Kim J, et al. Interaction of PIAS1 with PRRS virus nucleocapsid protein mediates NF-κB activation and triggers proinflammatory mediators during viral infection[J]. Sci Rep, 2019, 9(1): 11042. doi: 10.1038/s41598-019-47495-9 pmid: 31363150
[37]	Collins LV, Hajizadeh S, Holme E, et al. Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses[J]. J Leukoc Biol, 2004, 75(6): 995-1000. doi: 10.1189/jlb.0703328 URL
[38]	Shimada K, Crother TR, Karlin J, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis[J]. Immunity, 2012, 36(3): 401-414. doi: 10.1016/j.immuni.2012.01.009 pmid: 22342844
[39]	Shahid M, Gao J, Zhou YN, et al. Prototheca zopfii isolated from bovine mastitis induced oxidative stress and apoptosis in bovine mammary epithelial cells[J]. Oncotarget, 2017, 8(19): 31938-31947. doi: 10.18632/oncotarget.v8i19 URL
[40]	Fu SC, Liu JM, Lee KN, et al. Cr(VI)induces ROS-mediated mitochondrial-dependent apoptosis in neuronal cells via the activation of Akt/ERK/AMPK signaling pathway[J]. Toxicol In Vitro, 2020, 65: 104795. doi: 10.1016/j.tiv.2020.104795 URL
[41]	Wang HL, Xing GD, Qian Y, et al. Dihydromyricetin attenuates heat stress-induced apoptosis in dairy cow mammary epithelial cells through suppressing mitochondrial dysfunction[J]. Ecotoxicol Environ Saf, 2021, 214: 112078. doi: 10.1016/j.ecoenv.2021.112078 URL
[42]	Cheng J, Zhang J, Yang JY, et al. Klebsiella pneumoniae infection causes mitochondrial damage and dysfunction in bovine mammary epithelial cells[J]. Vet Res, 2021, 52(1): 17. doi: 10.1186/s13567-021-00898-x pmid: 33568211
[43]	Li YN, Zhu YH, Chu BX, et al. Map of enteropathogenic Escherichia coli targets mitochondria and triggers DRP-1-mediated mitochondrial fission and cell apoptosis in bovine mastitis[J]. Int J Mol Sci, 2022, 23(9): 4907. doi: 10.3390/ijms23094907 URL
[44]	Giordano C, Iommarini L, Giordano L, et al. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy[J]. Brain, 2014, 137(Pt 2): 335-353. doi: 10.1093/brain/awt343 pmid: 24369379
[45]	Leclercq IA, Farrell GC, Field J, et al. CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis[J]. J Clin Invest, 2000, 105(8): 1067-1075. doi: 10.1172/JCI8814 pmid: 10772651
[46]	Reid Thompson W, Hornby B, Manuel R, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism[J]. Genet Med, 2021, 23(3): 471-478. doi: 10.1038/s41436-020-01006-8 pmid: 33077895
[47]	Zhang Q, Zhang C, Ge J, et al. Ameliorative effects of resveratrol against cadmium-induced nephrotoxicity via modulating nuclear xenobiotic receptor response and PINK1/Parkin-mediated Mitophagy[J]. Food Funct, 2020, 11(2): 1856-1868. doi: 10.1039/c9fo02287b pmid: 32068207
[48]	Mok BY, de Moraes MH, Zeng J, et al. A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing[J]. Nature, 2020, 583(7817): 631-637. doi: 10.1038/s41586-020-2477-4
[49]	Tang X, Liu C, Li T, et al. Gambogic acid alleviates inflammation and apoptosis and protects the blood-milk barrier in mastitis induced by LPS[J]. Int Immunopharmacol, 2020, 86: 106697. doi: 10.1016/j.intimp.2020.106697 URL
[50]	Murphy MP, Smith RAJ. Targeting antioxidants to mitochondria by conjugation to lipophilic cations[J]. Annu Rev Pharmacol Toxicol, 2007, 47: 629-656. pmid: 17014364
[51]	Qiu LN, Luo YJ, Chen XJ. Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats[J]. Biomed Pharmacother, 2018, 103: 1585-1591. doi: S0753-3322(18)30545-6 pmid: 29864946
[52]	Wang XJ, Shen K, Wang J, et al. Hypoxic preconditioning combined with curcumin promotes cell survival and mitochondrial quality of bone marrow mesenchymal stem cells, and accelerates cutaneous wound healing via PGC-1α/SIRT3/HIF-1α signaling[J]. Free Radic Biol Med, 2020, 159: 164-176. doi: 10.1016/j.freeradbiomed.2020.07.023 URL