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Current Pharmaceutical Design

Author(s): Xu-Dong He, Fan Zhang, Ying Huang, Jun-Jie Hao, Mei Zhang, Jin-Biao He, Xue-Mei Pu, Yan-Juan Li, Lei Zi, Jie Yu* and Xing-Xin Yang*

DOI: 10.2174/1381612828666220520161200

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Potential Indicators of Mitochondrial Structure and Function

Page: [1738 - 1744] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Mitochondria regulate a range of important physiological and biochemical cellular processes including apoptotic cell death, energy production, calcium homeostasis, oxidative stress, and lipid metabolism. Given their role as the ‘engines’ of cells, their dysfunction is associated with a variety of disease states. Exploring the relationship between mitochondrial function and disease can reveal the mechanism(s) of drug activity and disease pathology. In this review, we summarized the methods of evaluating the structure and function of mitochondria, including the morphology, membrane fluidity, membrane potential, opening of the membrane permeability transition pore, inner membrane permeabilization, mitochondrial dynamics, mitophagy, oxidative stress, energy metabolism-related enzymes, apoptotic pathway related proteins, calcium concentration, DNA copy number, oxygen consumption, β-oxidation-related genes and proteins, cardiolipin content, and adenosine triphosphate content. We believe that the information presented in this review will help explore the pathological processes of mitochondria in the occurrence and development of diseases, as well as the activity and mechanism of drugs, and the discovery of new drugs.

Keywords: Disease, mechanism, drug, evaluation, method, mitochondria.

[1]
Torres-Sánchez ED, Pacheco-Moisés FP, Macias-Islas MA, et al. Effect of fish and olive oil on mitochondrial ATPase activity and membrane fluidity in patients with relapsing-remitting multiple sclerosis treated with interferon beta 1-b. Nutr Hosp 2018; 35(1): 162-8.
[PMID: 29565165]
[2]
Friedman JR, Nunnari J. Mitochondrial form and function. Nature 2014; 505(7483): 335-43.
[http://dx.doi.org/10.1038/nature12985 ] [PMID: 24429632]
[3]
Mu JK, Li YQ, Shi TT, et al. Remedying the mitochondria to cure human diseases by natural products. Oxid Med Cell Longev 2020; 2020: 5232614.
[http://dx.doi.org/10.1155/2020/5232614 ] [PMID: 32733635]
[4]
Zhao Y, Zhang Y, Zhang J, Yang G. Salvianolic acid B protects against MPP+-induced neuronal injury via repressing oxidative stress and restoring mitochondrial function. Neuroreport 2021; 32(9): 815-23.
[http://dx.doi.org/10.1097/WNR.0000000000001660 ] [PMID: 33994527]
[5]
Wang F, Ogasawara MA, Huang P. Small mitochondria-targeting molecules as anti-cancer agents. Mol Aspects Med 2010; 31(1): 75-92.
[http://dx.doi.org/10.1016/j.mam.2009.12.003 ] [PMID: 19995573]
[6]
Wu RM, Jiang B, Li H, et al. A network pharmacology approach to discover action mechanisms of Yangxinshi Tablet for improving energy metabolism in chronic ischemic heart failure. J Ethnopharmacol 2020; 246: 112227.
[http://dx.doi.org/10.1016/j.jep.2019.112227 ] [PMID: 31509780]
[7]
Luo Y, Wan Q, Xu M, et al. Nutritional preconditioning induced by astragaloside IV on isolated hearts and cardiomyocytes against myocardial ischemia injury via improving Bcl-2-mediated mitochondrial function. Chem Biol Interact 2019; 309: 108723.
[http://dx.doi.org/10.1016/j.cbi.2019.06.036 ] [PMID: 31228469]
[8]
Park A, Oh M, Lee SJ, et al. Mitochondrial transplantation as a novel therapeutic strategy for mitochondrial diseases. Int J Mol Sci 2021; 22(9): 4793.
[http://dx.doi.org/10.3390/ijms22094793 ] [PMID: 33946468]
[9]
Palmer CS, Anderson AJ, Stojanovski D. Mitochondrial protein import dysfunction: Mitochondrial disease, neurodegenerative disease and cancer. FEBS Lett 2021; 595(8): 1107-31.
[http://dx.doi.org/10.1002/1873-3468.14022 ] [PMID: 33314127]
[10]
Dard L, Blanchard W, Hubert C, Lacombe D, Rossignol R. Mitochondrial functions and rare diseases. Mol Aspects Med 2020; 71: 100842.
[http://dx.doi.org/10.1016/j.mam.2019.100842 ] [PMID: 32029308]
[11]
Shanmughapriya S, Langford D, Natarajaseenivasan K. Inter and Intracellular mitochondrial trafficking in health and disease. Ageing Res Rev 2020; 62: 101128.
[http://dx.doi.org/10.1016/j.arr.2020.101128 ] [PMID: 32712108]
[12]
Li L, Qi R, Zhang L, et al. Potential biomarkers and targets of mitochondrial dynamics. Clin Transl Med 2021; 11(8): e529.
[http://dx.doi.org/10.1002/ctm2.529 ] [PMID: 34459143]
[13]
Kumar S, Pan CC, Shah N, et al. Activation of Mitofusin2 by Smad2-RIN1 Complex during Mitochondrial Fusion. Mol Cell 2016; 62(4): 520-31.
[http://dx.doi.org/10.1016/j.molcel.2016.04.010 ] [PMID: 27184078]
[14]
Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC. Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 2003; 160(2): 189-200.
[http://dx.doi.org/10.1083/jcb.200211046 ] [PMID: 12527753]
[15]
Reddy PH. Inhibitors of mitochondrial fission as a therapeutic strategy for diseases with oxidative stress and mitochondrial dysfunction. J Alzheimers Dis 2014; 40(2): 245-56.
[http://dx.doi.org/10.3233/JAD-132060 ] [PMID: 24413616]
[16]
Chan DC. Mitochondrial Dynamics and its involvement in disease. Annu Rev Pathol 2020; 15(1): 235-59.
[http://dx.doi.org/10.1146/annurev-pathmechdis-012419-032711 ] [PMID: 31585519]
[17]
Peralta S, González-Quintana A, Ybarra M, et al. Novel ATAD3A recessive mutation associated to fatal cerebellar hypoplasia with multiorgan involvement and mitochondrial structural abnormalities. Mol Genet Metab 2019; 128(4): 452-62.
[http://dx.doi.org/10.1016/j.ymgme.2019.10.012 ] [PMID: 31727539]
[18]
Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res 2005; 8(1): 3-5.
[http://dx.doi.org/10.1089/rej.2005.8.3 ] [PMID: 15798367]
[19]
Tagaya M, Arasaki K. Regulation of mitochondrial dynamics and autophagy by the mitochondria-associated membrane. Adv Exp Med Biol 2017; 997: 33-47.
[http://dx.doi.org/10.1007/978-981-10-4567-7_3 ] [PMID: 28815520]
[20]
Hamacher-Brady A, Brady NR. Mitophagy programs: Mechanisms and physiological implications of mitochondrial targeting by autophagy. Cell Mol Life Sci 2016; 73(4): 775-95.
[http://dx.doi.org/10.1007/s00018-015-2087-8 ] [PMID: 26611876]
[21]
Aghadavod E, Khodadadi S, Baradaran A, Nasri P, Bahmani M, Rafieian-Kopaei M. Role of oxidative stress and inflammatory factors in diabetic kidney disease. Iran J Kidney Dis 2016; 10(6): 337-43.
[PMID: 27903991]
[22]
Sato S, Furuya N. Induction of PINK1/Parkin-Mediated Mitophagy. Methods Mol Biol 2018; 1759: 9-17.
[http://dx.doi.org/10.1007/7651_2017_7 ] [PMID: 28361482]
[23]
Serviddio G, Sastre J, Bellanti F, Viña J, Vendemiale G, Altomare E. Mitochondrial involvement in non-alcoholic steatohepatitis. Mol Aspects Med 2008; 29(1-2): 22-35.
[http://dx.doi.org/10.1016/j.mam.2007.09.014 ] [PMID: 18061659]
[24]
Xia C, Fu B, Zhang X, Qin C, Jin JC. Chitosan quaternary ammonium salt induced mitochondrial membrane permeability transition pore opening study in a spectroscopic perspective. Int J Biol Macromol 2020; 165(Pt A): 314-20.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.09.146] [PMID: 32987072]
[25]
Jin JC, Xu ZQ, Dong P, et al. One-step synthesis of silver nanoparticles using carbon dots as reducing and stabilizing agents and their anti-bacterial mechanisms. Carbon 2015; 94: 129-41.
[http://dx.doi.org/10.1016/j.carbon.2015.05.084]
[26]
Ricchelli F, Gobbo S, Moreno G, Salet C. Changes of the fluidity of mitochondrial membranes induced by the permeability transition. Biochemistry 1999; 38(29): 9295-300.
[http://dx.doi.org/10.1021/bi9900828 ] [PMID: 10413503]
[27]
Wang C, Wang G, Li X, et al. Highly sensitive fluorescence molecular switch for the ratio monitoring of trace change of mitochondrial membrane potential. Anal Chem 2017; 89(21): 11514-9.
[http://dx.doi.org/10.1021/acs.analchem.7b02781 ] [PMID: 28969416]
[28]
Yang XX, Liang L, Liu X, et al. Efficiently capturing mitochondria-targeted constituents with hepatoprotective activity from medicinal herbs. Oxid Med Cell Longev 2019; 2019: 4353791.
[http://dx.doi.org/10.1155/2019/4353791 ] [PMID: 31093314]
[29]
Brenner D, Mak TW. Mitochondrial cell death effectors. Curr Opin Cell Biol 2009; 21(6): 871-7.
[http://dx.doi.org/10.1016/j.ceb.2009.09.004 ] [PMID: 19822411]
[30]
Chalah A, Khosravi-Far R. The mitochondrial death pathway. Adv Exp Med Biol 2008; 615: 25-45.
[http://dx.doi.org/10.1007/978-1-4020-6554-5_3 ] [PMID: 18437890]
[31]
Ola MS, Nawaz M, Ahsan H. Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 2011; 351(1-2): 41-58.
[http://dx.doi.org/10.1007/s11010-010-0709-x ] [PMID: 21210296]
[32]
Filograna R, Mennuni M, Alsina D, Larsson NG. Mitochondrial DNA copy number in human disease: The more the better? FEBS Lett 2021; 595(8): 976-1002.
[http://dx.doi.org/10.1002/1873-3468.14021 ] [PMID: 33314045]
[33]
Don AS, Hogg PJ. Mitochondria as cancer drug targets. Trends Mol Med 2004; 10(8): 372-8.
[http://dx.doi.org/10.1016/j.molmed.2004.06.005 ] [PMID: 15310457]
[34]
Yang LY, Gao JL, Gao T, et al. Toxicity of polyhydroxylated fullerene to mitochondria. J Hazard Mater 2016; 301: 119-26.
[http://dx.doi.org/10.1016/j.jhazmat.2015.08.046 ] [PMID: 26348144]
[35]
Pedersen SF, Flinck M, Pardo LA. The interplay between dysregulated ion transport and mitochondrial architecture as a dangerous liaison in cancer. Int J Mol Sci 2021; 22(10): 5209.
[http://dx.doi.org/10.3390/ijms22105209 ] [PMID: 34069047]
[36]
Sies H. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress. Redox Biol 2017; 11: 613-9.
[http://dx.doi.org/10.1016/j.redox.2016.12.035 ] [PMID: 28110218]
[37]
Finkel T. Signal transduction by mitochondrial oxidants. J Biol Chem 2012; 287(7): 4434-40.
[http://dx.doi.org/10.1074/jbc.R111.271999 ] [PMID: 21832045]
[38]
Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991; 11(1): 81-128.
[http://dx.doi.org/10.1016/0891-5849(91)90192-6 ] [PMID: 1937131]
[39]
Liao W, Jin Q, Liu J, et al. Mahuang decoction antagonizes acute liver failure via modulating tricarboxylic acid cycle and amino acids metabolism. Front Pharmacol 2021; 12: 599180.
[http://dx.doi.org/10.3389/fphar.2021.599180 ] [PMID: 33859560]
[40]
Liu R, Chen L, Wang Z, et al. Omega-3 polyunsaturated fatty acids prevent obesity by improving tricarboxylic acid cycle homeostasis. J Nutr Biochem 2021; 88: 108503.
[http://dx.doi.org/10.1016/j.jnutbio.2020.108503 ] [PMID: 32956825]
[41]
Wolfe RR, Jahoor F. Recovery of labeled CO2 during the infusion of C-1- vs C-2-labeled acetate: Implications for tracer studies of substrate oxidation. Am J Clin Nutr 1990; 51(2): 248-52.
[http://dx.doi.org/10.1093/ajcn/51.2.248 ] [PMID: 2106256]
[42]
Baughn AD, Garforth SJ, Vilchèze C, Jacobs WR Jr. An anaerobic-type alpha-ketoglutarate ferredoxin oxidoreductase completes the oxidative tricarboxylic acid cycle of Mycobacterium tuberculosis. PLoS Pathog 2009; 5(11): e1000662.
[http://dx.doi.org/10.1371/journal.ppat.1000662 ] [PMID: 19936047]
[43]
Zhang S, Bryant DA. The tricarboxylic acid cycle in cyanobacteria. Science 2011; 334(6062): 1551-3.
[http://dx.doi.org/10.1126/science.1210858 ] [PMID: 22174252]
[44]
Area-Gomez E, Guardia-Laguarta C, Schon EA, Przedborski S. Mitochondria, OxPhos, and neurodegeneration: Cells are not just running out of gas. J Clin Invest 2019; 129(1): 34-45.
[http://dx.doi.org/10.1172/JCI120848 ] [PMID: 30601141]
[45]
Nakamoto RK, Baylis Scanlon JA, Al-Shawi MK. The rotary mechanism of the ATP synthase. Arch Biochem Biophys 2008; 476(1): 43-50.
[http://dx.doi.org/10.1016/j.abb.2008.05.004 ] [PMID: 18515057]
[46]
Zhang H, Chang Z, Mehmood K, et al. Nano copper induces apoptosis in PK-15 cells via a mitochondria-mediated pathway. Biol Trace Elem Res 2018; 181(1): 62-70.
[http://dx.doi.org/10.1007/s12011-017-1024-0 ] [PMID: 28497347]
[47]
Verma N, Pink M, Schmitz-Spanke S. A new perspective on calmodulin-regulated calcium and ROS homeostasis upon carbon black nanoparticle exposure. Arch Toxicol 2021; 95(6): 2007-18.
[http://dx.doi.org/10.1007/s00204-021-03032-0 ] [PMID: 33772346]
[48]
Larman TC, DePalma SR, Hadjipanayis AG, et al. Spectrum of somatic mitochondrial mutations in five cancers. Proc Natl Acad Sci USA 2012; 109(35): 14087-91.
[http://dx.doi.org/10.1073/pnas.1211502109 ] [PMID: 22891333]
[49]
Rahman S. Mitochondrial disease in children. J Intern Med 2020; 287(6): 609-33.
[http://dx.doi.org/10.1111/joim.13054 ] [PMID: 32176382]
[50]
Bratic I, Hench J, Henriksson J, Antebi A, Bürglin TR, Trifunovic A. Mitochondrial DNA level, but not active replicase, is essential for Caenorhabditis elegans development. Nucleic Acids Res 2009; 37(6): 1817-28.
[http://dx.doi.org/10.1093/nar/gkp018 ] [PMID: 19181702]
[51]
Ma L, Liu JY, Dong JX, Xiao Q, Zhao J, Jiang FL. Toxicity of Pb2+ on rat liver mitochondria induced by oxidative stress and mitochondrial permeability transition. Toxicol Res (Camb) 2017; 6(6): 822-30.
[http://dx.doi.org/10.1039/C7TX00204A ] [PMID: 30090545]
[52]
Yang XX, Wang X, Shi TT, et al. Mitochondrial dysfunction in high-fat diet-induced nonalcoholic fatty liver disease: The alleviating effect and its mechanism of Polygonatum kingianum. Biomed Pharmacother 2019; 117: 109083.
[http://dx.doi.org/10.1016/j.biopha.2019.109083 ] [PMID: 31387169]
[53]
Li LY, Li JM, Ning LJ, et al. Mitochondrial fatty acid β-oxidation inhibition promotes glucose utilization and protein deposition through energy homeostasis remodeling in fish. J Nutr 2020; 150(9): 2322-35.
[http://dx.doi.org/10.1093/jn/nxaa187 ] [PMID: 32720689]
[54]
Wicks SE, Vandanmagsar B, Haynie KR, et al. Impaired mitochondrial fat oxidation induces adaptive remodeling of muscle metabolism. Proc Natl Acad Sci USA 2015; 112(25): E3300-9.
[http://dx.doi.org/10.1073/pnas.1418560112 ] [PMID: 26056297]
[55]
Li LY, Samwel M. The metabolic regulation of dietary L‐carnitine in aquaculture nutrition: Present status and future research strategies, Reviews. In Aquaculture 2019; 11: 1228-57.
[56]
Bremer J. Carnitine--metabolism and functions. Physiol Rev 1983; 63(4): 1420-80.
[http://dx.doi.org/10.1152/physrev.1983.63.4.1420 ] [PMID: 6361812]
[57]
Gnoni A, Longo S, Gnoni GV, Giudetti AM. Carnitine in human muscle bioenergetics: can carnitine supplementation improve physical exercise? Molecules 2020; 25(1): 182.
[http://dx.doi.org/10.3390/molecules25010182 ] [PMID: 31906370]
[58]
Li JM, Li LY, Qin X, et al. Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio. Sci Rep 2017; 7(1): 40815.
[http://dx.doi.org/10.1038/srep40815 ] [PMID: 28102299]
[59]
Wu H, Li X, Shen C. Peroxisome proliferator-activated receptor gamma in white and brown adipocyte regulation and differentiation. Physiol Res 2020; 69(5): 759-73.
[http://dx.doi.org/10.33549/physiolres.934411 ] [PMID: 32901494]
[60]
Montesinos J, Area-Gomez E, Schlame M. Analysis of phospholipid synthesis in mitochondria. Methods Cell Biol 2020; 155: 321-35.
[http://dx.doi.org/10.1016/bs.mcb.2019.12.003 ] [PMID: 32183965]
[61]
El-Hafidi M, Correa F, Zazueta C. Mitochondrial dysfunction in metabolic and cardiovascular diseases associated with cardiolipin remodeling. Biochim Biophys Acta Mol Basis Dis 2020; 1866(6): 165744.
[http://dx.doi.org/10.1016/j.bbadis.2020.165744 ] [PMID: 32105822]
[62]
Mahajan N, Hoover B, Rajendram M, et al. Maspin binds to cardiolipin in mitochondria and triggers apoptosis. FASEB J 2019; 33(5): 6354-64.
[http://dx.doi.org/10.1096/fj.201802182R ] [PMID: 30786218]
[63]
Ducasa GM, Mitrofanova A, Mallela SK, et al. ATP-binding cassette A1 deficiency causes cardiolipin-driven mitochondrial dysfunction in podocytes. J Clin Invest 2019; 129(8): 3387-400.
[http://dx.doi.org/10.1172/JCI125316 ] [PMID: 31329164]
[64]
Yang F, Pei R, Zhang Z, et al. Copper induces oxidative stress and apoptosis through mitochondria-mediated pathway in chicken hepatocytes. Toxicol In Vitro 2019; 54: 310-6.
[http://dx.doi.org/10.1016/j.tiv.2018.10.017 ] [PMID: 30389602]
[65]
Jin S, Hao Y, Zhu Z, et al. Impact of mitochondrion-targeting group on the reactivity and cytostatic pathway of platinum(IV) complexes. Inorg Chem 2018; 57(17): 11135-45.
[http://dx.doi.org/10.1021/acs.inorgchem.8b01707 ] [PMID: 30117731]
[66]
Takeuchi Y, Morii H, Tamura M, Hayaishi O, Watanabe Y. A possible mechanism of mitochondrial dysfunction during cerebral ischemia: Inhibition of mitochondrial respiration activity by arachidonic acid. Arch Biochem Biophys 1991; 289(1): 33-8.
[http://dx.doi.org/10.1016/0003-9861(91)90438-O ] [PMID: 1654847]
[67]
Canevari L, Clark JB, Bates TE. beta-Amyloid fragment 25-35 selectively decreases complex IV activity in isolated mitochondria. FEBS Lett 1999; 457(1): 131-4.
[http://dx.doi.org/10.1016/S0014-5793(99)01028-5 ] [PMID: 10486579]
[68]
Zhang HX, Du GH, Zhang JT. Assay of mitochondrial functions by resazurin in vitro. Acta Pharmacol Sin 2004; 25(3): 385-9.
[PMID: 15000895]