Mitochondrial Proton Leak Plays a Critical Role in Pathogenesis of Cardiovascular Diseases
Open accessAbstract
Mitochondrial proton leak is the principal mechanism that incompletely couples substrate oxygen to ATP generation. This chapter briefly addresses the recent progress made in understanding the role of proton leak in the pathogenesis of cardiovascular diseases. Majority of the proton conductance is mediated by uncoupling proteins (UCPs) located in the mitochondrial inner membrane. It is evident that the proton leak and reactive oxygen species (ROS) generated from electron transport chain (ETC) in mitochondria are linked to each other. Increased ROS production has been shown to induce proton conductance, and in return, increased proton conductance suppresses ROS production, suggesting the existence of a positive feedback loop that protects the biological systems from detrimental effects of augmented oxidative stress. There is mounting evidence attributing to proton leak and uncoupling proteins a crucial role in the pathogenesis of cardiovascular disease. We can surmise the role of "uncoupling" in cardiovascular disorders as follows; First, the magnitude of the proton leak and the mechanism involved in mediating the proton leak determine whether there is a protective effect against ischemia-reperfusion (IR) injury. Second, uncoupling by UCP2 preserves vascular function in diet-induced obese mice as well as in diabetes. Third, etiology determines whether the proton conductance is altered or not during hypertension. And fourth, proton leak regulates ATP synthesis-uncoupled mitochondrial ROS generation, which determines pathological activation of endothelial cells for recruitment of inflammatory cells. Continue effort in improving our understanding in the role of proton leak in the pathogenesis of cardiovascular and metabolic diseases would lead to identification of novel therapeutic targets for treatment.
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Increased proton leak is directly related to the prevention of oxidative stress, the inhibition of fatty acid induced mitochondrial damage and the control of oxidative phosphorylation, potentially protecting the cell from excessive damage.
“It has been suggested that increased proton leak is directly related to the prevention of oxidative stress, the inhibition of fatty acid induced mitochondrial damage and the control of oxidative phosphorylation [25], potentially protecting the cell from excessive damage.”
From Heterozygous expression of the Alzheimer’s disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses (2022) · cites this paper as [25]
The ‘ROS Generation and Proton Leak’ section says enhanced proton leak can reduce ROS production and limit further mitochondrial damage. The section on coupling oxygen consumption to ATP generation explains how proton leak affects oxidative phosphorylation. Our copy does not say that increased leak inhibits fatty-acid-induced mitochondrial damage; the section on ischemia–reperfusion injury also cautions that larger leaks can be harmful. (LLM, conf=0.86)
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Cites
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207 · see citing works
Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism
MITCHELL, P. (1961) · Nature · doi:10.1038/191144a0 · Cited by 4,704 · see citing works
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S.-I., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H.-P., et al. (2000) · Nature · doi:10.1038/35008121 · Cited by 4,277 · see citing works
Boveris, A., & Chance, B. (1973) · Biochemical Journal · doi:10.1042/bj1340707 · Cited by 2,626 · see citing works
The mitochondrial permeability transition pore and its role in cell death
CROMPTON, M. (1999) · Biochemical Journal · doi:10.1042/bj3410233 · Cited by 2,432 · see citing works
Direct observation of the rotation of F1-ATPase
Noji, H., Yasuda, R., Yoshida, M., & Kinosita, K. (1997) · Nature · doi:10.1038/386299a0 · Cited by 2,216 · see citing works
Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria
Turrens, J. F., & Boveris, A. (1980) · Biochemical Journal · doi:10.1042/bj1910421 · Cited by 1,601 · see citing works
Mechanisms Underlying Acute Protection From Cardiac Ischemia-Reperfusion Injury
Murphy, E., & Steenbergen, C. (2008) · Physiological Reviews · doi:10.1152/physrev.00024.2007 · Cited by 1,472 · see citing works
Superoxide activates mitochondrial uncoupling proteins
Echtay, K. S., Roussel, D., St-Pierre, J., Jekabsons, M. B., Cadenas, S., Stuart, J. A., Harper, J. A., Roebuck, S. J., Morrison, A., Pickering, S., et al. (2002) · Nature · doi:10.1038/415096a · Cited by 1,382 · see citing works
RESPIRATORY ENZYMES IN OXIDATIVE PHOSPHORYLATION
Chance, B., & Williams, G. R. (1955) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)57191-5 · Cited by 1,125 · see citing works
Arsenijevic, D., Onuma, H., Pecqueur, C., Raimbault, S., Manning, B. S., Miroux, B., Couplan, E., Alves‐Guerra, M., Goubern, M., Surwit, R. S., et al. (2000) · Nature Genetics · doi:10.1038/82565 · Cited by 1,079 · see citing works
Li, X., Fang, P., Mai, J., Choi, E. T., Wang, H., & Yang, X. (2013) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-6-19 · Cited by 810 · see citing works
Self-citationSpeakman, J. R., Talbot, D. A., Selman, C., Snart, S., McLaren, J. S., Redman, P., Krol, E., Jackson, D. M., Johnson, M. S., & Brand, M. D. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00097.x · Cited by 761 · see citing works
Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species
Starkov, A. A., Fiskum, G. M., Chinopoulos, C., Lorenzo, B. J., Browne, S. E., Patel, M. S., & Beal, M. F. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1899-04.2004 · Cited by 692 · see citing works
Energy metabolism in uncoupling protein 3 gene knockout mice
Vidal-Puig, A. J., Grujic, D., Zhang, C.-Y., Hagen, T., Boss, O., Ido, Y., Szczepanik, A., Wade, J., Mootha, V., Cortright, R., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910179199 · Cited by 677 · see citing works
Mitochondrial calcium overload is a key determinant in heart failure
Santulli, G., Xie, W., Reiken, S. R., & Marks, A. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1513047112 · Cited by 561 · see citing works
Regulation of brain mitochondrial H 2 O 2 production by membrane potential and NAD(P)H redox state
Starkov, A. A., & Fiskum, G. M. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01908.x · Cited by 491 · see citing works
Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes
Green, K., Brand, M. D., & Murphy, M. P. (2004) · Diabetes · doi:10.2337/diabetes.53.2007.s110 · Cited by 490 · see citing works
Intrinsic and extrinsic uncoupling of oxidative phosphorylation
Kadenbach, B. (2003) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(03)00027-6 · Cited by 486 · see citing works
Mitochondrial H + Leak and ROS Generation: An Odd Couple
Brookes, P. S. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.10.016 · Cited by 447 · see citing works
The basal proton conductance of mitochondria depends on adenine nucleotide translocase content
Brand, M. D., Pakay, J. L., Ocloo, A., Kokoszka, J., Wallace, D. C., Brookes, P. S., & Cornwall, E. J. (2005) · Biochemical Journal · doi:10.1042/bj20050890 · Cited by 410 · see citing works
Hill, B. G., Dranka, B. P., Zou, L., Chatham, J. C., & Darley-Usmar, V. M. (2009) · Biochemical Journal · doi:10.1042/bj20090934 · Cited by 284 · see citing works
Pfleger, J. M., He, M., & Abdellatif, M. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.202 · Cited by 251 · see citing works
BRENNAN, J., SOUTHWORTH, R., MEDINA, R., DAVIDSON, S., DUCHEN, M., & SHATTOCK, M. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.07.019 · Cited by 242 · see citing works
Protective Role of Uncoupling Protein 2 in Atherosclerosis
Blanc, J., Alves‐Guerra, M., Esposito, B., Rousset, S., Gourdy, P., Ricquier, D., Tedgui, A., Miroux, B., & Mallat, Z. (2003) · Circulation · doi:10.1161/01.cir.0000051722.66074.60 · Cited by 239 · see citing works
The on-off switches of the mitochondrial uncoupling proteins
Azzu, V., & Brand, M. D. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.11.001 · Cited by 239 · see citing works
Brookes, P. S., Buckingham, J. A., Tenreiro, A. M., Hulbert, A. J., & Brand, M. D. (1998) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/s0305-0491(97)00357-x · Cited by 238 · see citing works
The mitochondrial respiratory chain
Rich, P. R., & Maréchal, A. (2010) · Essays in Biochemistry · doi:10.1042/bse0470001 · Cited by 237 · see citing works
Goffart, S., VONKLEISTRETZOW, J., & Wiesner, R. H. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.06.030 · Cited by 176 · see citing works
Slip and leak in mitochondrial oxidative phosphorylation
Murphy, M. P. (1989) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(89)80063-5 · Cited by 170 · see citing works
Minners, J. (2000) · Cardiovascular Research · doi:10.1016/s0008-6363(00)00069-9 · Cited by 163 · see citing works
Herrero, A., & Barja, G. (1997) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1022458010266 · Cited by 152 · see citing works
Lee, K.-U., Lee, I. K., Han, J., Song, D., Kim, Y., Song, H. S., Kim, H. S., Lee, W. J., Koh, E. H., Song, K., et al. (2005) · Circulation Research · doi:10.1161/01.res.0000170075.73039.5b · Cited by 147 · see citing works
Mitoguardin regulates mitochondrial fusion through MitoPLD and is required for neuronal homeostasis.
Zhang, Y., Liu, X., Bai, J., Tian, X., Zhao, X., Liu, W., Duan, X., Shang, W., Fan, H.-Y., & Tong, C. (2016) · Molecular Cell · doi:10.1016/j.molcel.2015.11.017 · Cited by 145 · see citing works
Uncoupling Protein-2 Protects Endothelial Function in Diet-Induced Obese Mice
Tian, X. Y., Wong, W. T., Xu, A., Lu, Y., Zhang, Y., Wang, L., Cheang, W. S., Wang, Y., Yao, X., & Huang, Y. (2012) · Circulation Research · doi:10.1161/circresaha.111.262170 · Cited by 139 · see citing works
Self-citationPeroxynitrite and Brain Mitochondria: Evidence for Increased Proton Leak
Brookes, P. S., Land, J. M., Clark, J. B., & Heales, S. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052195.x · Cited by 125 · see citing works
Nadtochiy, S. M., Tompkins, A. J., & Brookes, P. S. (2006) · Biochemical Journal · doi:10.1042/bj20051927 · Cited by 123 · see citing works
Mitochondrial Respiratory Chain
Xu, J.-X., Xun, L., Yi-xin, Z., & He-yong, S. (1996) · AOCS Publishing eBooks · doi:10.1201/9781439832059.ch54 · Cited by 123 · see citing works
Wang, L., Yu, T., Lee, H., O'Brien, D. K., Sesaki, H., & Yoon, Y. (2015) · Cardiovascular Research · doi:10.1093/cvr/cvv005 · Cited by 119 · see citing works
Self-citationHaslip, M., Dostanic, I., Huang, Y., Zhang, Y., Russell, K. S., Jurczak, M. J., Mannam, P., Giordano, F. J., ERZURUM, S. C., & Lee, P. J. (2015) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304865 · Cited by 115 · see citing works
Ganote, C. E. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00114-7 · Cited by 85 · see citing works
Li, X., Fang, P., Yang, W. Y., Chan, K., Lavallee, M., Xu, K., Gao, T., Wang, H., & Yang, X. (2016) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2016-0515 · Cited by 77 · see citing works
Self-citationStimulation of mitochondrial proton conductance by hydroxynonenal requires a high membrane potential
Parker, N., Vidal‐Puig, A., & Brand, M. D. (2008) · Bioscience Reports · doi:10.1042/bsr20080002 · Cited by 67 · see citing works
Eirin, A., Ebrahimi, B., Kwon, S. H., Fiala, J. A., WILLIAMS, B. J., Woollard, J. R., He, Q., Gupta, R. C., Sabbah, H. N., Prakash, Y. S., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.115.003118 · Cited by 67 · see citing works
Fontaine, E. M., Moussa, M., Devin, A., Garcia, J., Ghisolfi, J., Rigoulet, M., & Leverve, X. M. (1996) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(96)00075-8 · Cited by 65 · see citing works
Zhu, X., Zuo, L., Cardounel, A. J., Zweier, J. L., & He, G. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.1389 · Cited by 60 · see citing works
A Hypertension-Associated tRNAAla Mutation Alters tRNA Metabolism and Mitochondrial Function
Jiang, P., Wang, M., Xue, L., Xiao, Y., Yu, J., Wang, H., Yao, J., Liu, H., Peng, Y., Liu, H., et al. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00199-16 · Cited by 59 · see citing works
Self-citationQuit smoking to outsmart atherogenesis: Molecular mechanisms underlying clinical evidence
Gambardella, J., Sardu, C., Sacra, C., Giudice, C. D., & Santulli, G. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.12.010 · Cited by 56 · see citing works
Kozieł, A., Broniarek, I., & Jarmuszkiewicz, W. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00759.2014 · Cited by 53 · see citing works
Quarrie, R., Cramer, B., Lee, D. S., Steinbaugh, G. E., Erdahl, W. L., Pfeiffer, D. R., Zweier, J. L., & Crestanello, J. A. (2010) · Journal of Surgical Research · doi:10.1016/j.jss.2010.09.018 · Cited by 37 · see citing works
Gómez‐Hernández, A., Perdomo, L., Heras, N. D. L., Beneit, N., Escribano, Ó., Otero, Y. F., Guillén, C., Díaz-Castroverde, S., Gozalbo-López, B., Cachofeiro, V., et al. (2014) · Cardiovascular Diabetology · doi:10.1186/s12933-014-0108-9 · Cited by 22 · see citing works
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Bøtker, H. E., Hausenloy, D. J., Andreadou, I., Antonucci, S., Boengler, K., Davidson, S. M., Deshwal, S., Devaux, Y., Lisa, F. D., Sante, M. D., et al. (2018) · Basic Research in Cardiology · doi:10.1007/s00395-018-0696-8 · Cited by 426 · see citing works
Vascular Endothelial Cells and Innate Immunity
Shao, Y., Saredy, J., Yang, W. Y., Sun, Y., Lu, Y., Saaoud, F., Drummer, C., Johnson, C., Xu, K., Jiang, X., et al. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.314330 · Cited by 302 · see citing works
Self-citationSun, Y., Lu, Y., Saredy, J., Wang, X., Drummer, C., Shao, Y., Saaoud, F., Xu, K., Liu, M., Yang, W. Y., et al. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101696 · Cited by 283 · see citing works
Self-citationSaaoud, F., Liu, L., Xu, K., Cueto, R., Shao, Y., Lu, Y., Sun, Y., Snyder, N. W., Wu, S., Yang, L., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.158183 · Cited by 153 · see citing works
Self-citationMitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling
Ježek, P., Holendová, B., Garlid, K., & Jabůrek, M. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7225 · Cited by 138 · see citing works
Saaoud, F., Charles Drummer, I. V., Shao, Y., Sun, Y., Lu, Y., Xu, K., Ni, D., Jiang, X., Wang, H., & Yang, X. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107715 · Cited by 121 · see citing works
Self-citationMechanisms of obesity-induced metabolic and vascular dysfunctions
Caldwell, R. W. (2019) · Frontiers in bioscience · doi:10.2741/4758 · Cited by 112 · see citing works
Li, X., Wang, L., Fang, P., Sun, Y., Jiang, X., Wang, H., & Yang, X. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002752 · Cited by 100 · see citing works
Self-citationNanayakkara, G., Wang, H., & Yang, X. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.12.002 · Cited by 95 · see citing works
Self-citationUncoupling Protein 2 in Cardiovascular Health and Disease
Tian, X. Y., Ma, S., Tse, G., Wong, W. T., & Huang, Y. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01060 · Cited by 93 · see citing works
Li, X., Fang, P., Sun, Y., Shao, Y., Yang, W. Y., Jiang, X., Wang, H., & Yang, X. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101373 · Cited by 88 · see citing works
Self-citationKoklesová, L., Mazuráková, A., Samec, M., Kúdela, E., Biringer, K., Kubatka, P., & Golubnitschaja, O. (2022) · The EPMA Journal · doi:10.1007/s13167-022-00281-6 · Cited by 85 · see citing works
Mitochondrial quality control in health and cardiovascular diseases
Atici, A. E., Crother, T. R., & Rivas, M. N. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1290046 · Cited by 83 · see citing works
Drummer, C., Saaoud, F., Jhala, N. C., Cueto, R., Sun, Y., Xu, K., Shao, Y., Lu, Y., Shen, H., Yang, L., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1113883 · Cited by 77 · see citing works
Self-citationShao, Y., Saredy, J., Xu, K., Sun, Y., Saaoud, F., Drummer, C., Lu, Y., Luo, J. J., Lopez‐Pastrana, J., Choi, E. T., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.653110 · Cited by 72 · see citing works
Self-citationMitochondrial redox and TCA cycle metabolite signaling in the heart
Vujić, A., Koo, A., Prag, H. A., & Krieg, T. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.02.041 · Cited by 62 · see citing works
Martínez‐Klimova, E., Aparicio‐Trejo, O. E., Gómez‐Sierra, T., Jiménez‐Uribe, A. P., Bellido, B., & Pedraza‐Chaverrí, J. (2020) · BioFactors · doi:10.1002/biof.1673 · Cited by 61 · see citing works
The potential mechanism of mitochondrial dysfunction in septic cardiomyopathy
Pan, P., Wang, X., & Liu, D. (2018) · Journal of International Medical Research · doi:10.1177/0300060518765896 · Cited by 58 · see citing works
Liao, J., He, W., Li, L., Wang, J., Gong, L., Zhang, Q., & Lin, Z. (2025) · Cell Biomaterials · doi:10.1016/j.celbio.2025.100016 · Cited by 62 · see citing works
Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature
Cho, Y. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105637 · Cited by 53 · see citing works
Zhang, J., Riquelme, M. A., Hua, R., Acosta, F. M., Gu, S., & Jiang, J. X. (2022) · eLife · doi:10.7554/elife.82206 · Cited by 51 · see citing works
A mechanism for increased sensitivity of acute myeloid leukemia to mitotoxic drugs
Panina, S., Baran, N., da Costa, F. H. B., Konopleva, M. Y., & Kirienko, N. V. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1851-3 · Cited by 50 · see citing works
A new paradigm in intracellular immunology: Mitochondria emerging as leading immune organelles
Xu, K., Saaoud, F., Shao, Y., Lu, Y., Yang, Q., Jiang, X., Wang, H., & Yang, X. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103331 · Cited by 49 · see citing works
Self-citationMarín-Royo, G., Gallardo, I., Martínez-Martínez, E., Gutiérrez, B., Jurado-López, R., López-Andrés, N., Gutiérrez-Tenorio, J., Rial, E., Bartolomé, M., Nieto, M., et al. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.032086 · Cited by 45 · see citing works
Pecorelli, A., Ferrara, F., Messano, N., Cordone, V., Schiavone, M. L., Cervellati, F., Woodby, B. L., Cervellati, C., Hayek, J., & Valacchi, G. (2020) · The FASEB Journal · doi:10.1096/fj.201902677r · Cited by 47 · see citing works
Lue, Y., Gao, C., Swerdloff, R. S., Hoang, J., Avetisyan, R., Jia, Y., Rao, M., Ren, S. V., Atienza, V., Yu, J., et al. (2018) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00155.2018 · Cited by 46 · see citing works
Approaching Inflammation Paradoxes—Proinflammatory Cytokine Blockages Induce Inflammatory Regulators
Liu, M., Saredy, J., Zhang, R., Shao, Y., Sun, Y., Yang, W. Y., Wang, J., Liu, L., Drummer, C., Johnson, C., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.554301 · Cited by 46 · see citing works
Self-citationHelliwell, A., Sweetman, E., Stockwell, P. A., Edgar, C. D., Chatterjee, A., & Tate, W. P. (2020) · Clinical Epigenetics · doi:10.1186/s13148-020-00960-z · Cited by 48 · see citing works
Leman, G., Pavel, P., Hermann, M., Crumrine, D. A., Elias, P. M., Minzaghi, D., Goudounèche, D., Prieto, N. M. R., Cavinato, M. S., Wanner, A., et al. (2022) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2022.01.035 · Cited by 43 · see citing works
Guerrero-Encinas, I., González-González, J. N., Santiago‐López, L., Muhlia‐Almazán, A., Garcia, H. S., Mazorra-Manzano, M. A., Vallejo‐Córdoba, B., González-Córdova, A. F., & Hernández‐Mendoza, A. (2021) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-021-09747-x · Cited by 43 · see citing works
Louwagie, E. J., Larsen, T. D., Wachal, A. L., Gandy, T. C. T., & Baack, M. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052382 · Cited by 43 · see citing works
Ren, H., Hu, W., Jiang, T., Yao, Q., Qi, Y., & Huang, K. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116545 · Cited by 39 · see citing works
Okoye, C. N., MacDonald-Jay, N., & Kamunde, C. (2019) · Aquatic Toxicology · doi:10.1016/j.aquatox.2019.105264 · Cited by 40 · see citing works
Inflammatory mechanisms and intervention strategies for sepsis‐induced myocardial dysfunction
Nong, Y., Wei, X., & Yu, D. (2023) · Immunity Inflammation and Disease · doi:10.1002/iid3.860 · Cited by 37 · see citing works
Raj, P. S., Nair, A., Rani, M. R. P., Rajankutty, K., Ranjith, S., & Raghu, K. G. (2022) · International Journal of Cardiology · doi:10.1016/j.ijcard.2022.12.003 · Cited by 38 · see citing works
Liu, M., Xu, K., Saaoud, F., Shao, Y., Zhang, R., Lu, Y., Sun, Y., Drummer, C., Li, L., Wu, S., et al. (2022) · Journal of Immunology Research · doi:10.1155/2022/1433323 · Cited by 38 · see citing works
Self-citationAdzigbli, L., Sokolov, E. P., Wimmers, K., Sokolova, I. M., & Ponsuksili, S. (2022) · Scientific Reports · doi:10.1038/s41598-022-24386-0 · Cited by 38 · see citing works
Pathophysiological Basis for Nutraceutical Supplementation in Heart Failure: A Comprehensive Review
Mollace, V., Rosano, G. M. C., Anker, S. D., Coats, A. J. S., Seferovic, P. M., Mollace, R., Tavernese, A., Gliozzi, M., Musolino, V., Carresi, C., et al. (2021) · Nutrients · doi:10.3390/nu13010257 · Cited by 34 · see citing works
Impact of β-glycerophosphate on the bioenergetic profile of vascular smooth muscle cells
Alesutan, I., Moritz, F., Haider, T., Sun, S., Gollmann‐Tepeköylü, C., Holfeld, J., Pieske, B. M., Lang, F. J. W., Eckardt, K., Heinzmann, S. S., et al. (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01925-8 · Cited by 35 · see citing works
Magi, S., Preziuso, A., Piccirillo, S., Giampieri, F., Cianciosi, D., Orciani, M., & Amoroso, S. (2021) · Cells · doi:10.3390/cells10082109 · Cited by 35 · see citing works
Lu, Y., Nanayakkara, G., Sun, Y., Liu, L., Xu, K., Drummer, C., Shao, Y., Saaoud, F., Choi, E. T., Jiang, X., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102142 · Cited by 34 · see citing works
Self-citationHuynh, T. V., Rethi, L., Lee, T., Higa, S., Kao, Y., & Chen, Y. (2023) · Cells · doi:10.3390/cells12060877 · Cited by 37 · see citing works
Saaoud, F., Lu, Y., Xu, K., Shao, Y., Praticò, D., Vázquez-Padrón, R. I., Wang, H., & Yang, X. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108604 · Cited by 33 · see citing works
Self-citationSchulz, R., & Schlüter, K. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076459 · Cited by 33 · see citing works
Lu, Y., Sun, Y., Xu, K., Saaoud, F., Shao, Y., Drummer, C., Wu, S., Hu, W., Yu, J., Kunapuli, S. P., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.858256 · Cited by 32 · see citing works
Self-citationMitochondrial bioenergetic changes during development as an indicator of C. elegans health-span
Maglioni, S., Mello, D. F., Schiavi, A., Meyer, J. N., & Ventura, N. (2019) · Aging · doi:10.18632/aging.102208 · Cited by 29 · see citing works
Liu, X., Wang, Q., Li, X., Yang, Y., Deng, Y., Wang, X., Wang, P., Chen, L., Ma, L., & Shan, G. (2025) · Circulation · doi:10.1161/circulationaha.124.070840 · Cited by 29 · see citing works
Effects of Moringa oleifera Leaves Extract on High Glucose-Induced Metabolic Changes in HepG2 Cells
Gutiérrez, J. A. S., Valdez-Solana, M. A., Forbes-Hernández, T. Y., Avitia-Domínguez, C. I., García-Vargas, G. G., Salas-Pacheco, J. M., Flores-Herrera, Ó., Téllez‐Valencia, A., Battino, M. A., & Sierra‐Campos, E. (2018) · Biology · doi:10.3390/biology7030037 · Cited by 28 · see citing works
Shaw, G. A., Hyer, M. M., Targett, I. L., Dyer, S. K., Turkson, S., Burns, C. M., & Neigh, G. N. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.05.021 · Cited by 28 · see citing works
Mussalo, L., Lampinen, R., Avesani, S., Závodná, T., Krejčík, Z., Kalapudas, J., Penttilä, E., Löppönen, H., Koivisto, A. M., Malm, T., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103272 · Cited by 27 · see citing works
miR-150-PTPMT1-cardiolipin signaling in pulmonary arterial hypertension
Russomanno, G., Jo, K. B., Abdul‐Salam, V. B., Morgan, C. C., Endruschat, J., Schaeper, U., Osman, A. H., Alzaydi, M. M., Wilkins, M. R., & Wójciak‐Stothard, B. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.10.042 · Cited by 27 · see citing works
Antioxidant prevents clearance of hemostatically competent platelets after long‐term cold storage
Hegde, S., Wellendorf, A. M., Zheng, Y., & Cancelas, J. A. (2020) · Transfusion · doi:10.1111/trf.16200 · Cited by 26 · see citing works
Xu, K., Shao, Y., Saaoud, F., Gillespie, A., Drummer, C., Liu, L., Lu, Y., Sun, Y., Xi, H., Tükel, Ç., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.773473 · Cited by 26 · see citing works
Self-citationXu, K., Saaoud, F., Shao, Y., Lu, Y., Wu, S., Zhao, H., Chen, K., Vázquez-Padrón, R. I., Jiang, X., Wang, H., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102771 · Cited by 26 · see citing works
Self-citationSULT4A1 Protects Against Oxidative-Stress Induced Mitochondrial Dysfunction in Neuronal Cells
Hossain, M. I., Marcus, J. M., Lee, J. H., Garcia, P. L., Gagné, J., Poirier, G. G., Falany, C. N., & Andrabi, S. A. (2019) · Drug Metabolism and Disposition · doi:10.1124/dmd.119.088047 · Cited by 25 · see citing works
Elkin, E. R., Bridges, D., & Loch-Caruso, R. K. (2019) · Toxicology · doi:10.1016/j.tox.2019.152283 · Cited by 25 · see citing works
Scheuffele, H., Rubio‐Gracia, F., & Clark, T. D. (2021) · Journal of Experimental Biology · doi:10.1242/jeb.243504 · Cited by 24 · see citing works
Saito, E. R., Warren, C. E., Hanegan, C. M., Larsen, J. G., du Randt, J. D., Cannon, M. E., Saito, J. Y., Campbell, R. J., Kemberling, C. M., Miller, G., et al. (2022) · Metabolites · doi:10.3390/metabo12111019 · Cited by 24 · see citing works
Magrì, A., Cubisino, S. A. M., Battiato, G., Lipari, C. L. R., Nibali, S. C., Saab, M. W., Pittalà, A., Amorini, A. M., Pinto, V. D., & Messina, A. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043687 · Cited by 24 · see citing works
Kiernan, K., Alwarawrah, Y., Nichols, A., Danzaki, K., & MacIver, N. J. (2024) · Scientific Reports · doi:10.1038/s41598-024-54836-w · Cited by 24 · see citing works
Zeng, H., Nanayakkara, G., Shao, Y., Fu, H., Sun, Y., Cueto, R., Yang, W. Y., Yang, Q., Sheng, H., Wu, N., et al. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00516 · Cited by 24 · see citing works
Self-citationSolomon, S., Sampathkumar, N. K., Carre, I., Mondal, M., Chennell, G., Vernon, A. C., Ruepp, M.-D., & Mitchell, J. C. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04473-1 · Cited by 23 · see citing works
“It has been suggested that increased proton leak is directly related to the prevention of oxidative stress, the inhibition of fatty acid induced mitochondrial damage and the control of oxidative phosphorylation [25], potentially protecting the cell from excessive damage.”
BackgroundMetabolic reprogramming and dysregulated IL-17 production impairs CD4 T cell function post sepsis
de Assis, P. A., Allen, R., Schaller, M. A., Kunkel, S. L., & Bermick, J. (2024) · iScience · doi:10.1016/j.isci.2024.110114 · Cited by 23 · see citing works
Liu, M., Wu, N., Xu, K., Saaoud, F., Vasilopoulos, E., Shao, Y., Zhang, R., Wang, J., Shen, H., Yang, W. Y., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.713170 · Cited by 22 · see citing works
Self-citationGroen, C. M., Podratz, J. L., Pathoulas, J., Staff, N. P., & Windebank, A. J. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.1479-20.2021 · Cited by 23 · see citing works
Faulkner, A., Tamiato, A., Cathery, W., Rampin, A., Caravaggi, C. M. F., Jover, E., Allen, S., Mellor, H., Hauton, D., Heather, L. C., et al. (2020) · Diabetologia · doi:10.1007/s00125-020-05230-4 · Cited by 23 · see citing works
Comelli, M., Pretis, I., Buso, A., & Mavelli, I. (2017) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-017-9737-5 · Cited by 22 · see citing works
Kozal, J. S., Jayasundara, N., Massarsky, A., Lindberg, C. D., Oliveri, A. N., Cooper, E. M., Levin, E. D., Meyer, J. N., & Giulio, R. T. D. (2023) · Aquatic Toxicology · doi:10.1016/j.aquatox.2023.106658 · Cited by 22 · see citing works
Sun, Y., Yang, Z.-X., Ren, F., & Fang, B. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.04.186 · Cited by 22 · see citing works
Mule, R. D., Roy, R., Mandal, K., Chopra, D., Dutta, T., Sancheti, S. P., Shinde, P. S., Banerjee, S., Koner, A. L., Bhowal, R., et al. (2022) · Chemistry - A European Journal · doi:10.1002/chem.202200632 · Cited by 20 · see citing works
Hegde, S., Poojary, K. K., Rasquinha, R., Crasta, D. N., Gopalan, D., Mutalik, S., Siddiqui, S., Adiga, S. K., & Kalthur, G. (2020) · Pesticide Biochemistry and Physiology · doi:10.1016/j.pestbp.2020.104588 · Cited by 20 · see citing works
Fu, H., Sun, Y., Shao, Y., Saredy, J., Cueto, R., Liu, L., Drummer, C., Johnson, C., Xu, K., Lu, Y., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.595813 · Cited by 19 · see citing works
Self-citationSmolka, C., Schlösser, D., Koentges, C., Tarkhnishvili, A., Gorka, O., Pfeifer, D., Bemtgen, X., Asmussen, A., Groß, O., Diehl, P., et al. (2021) · The FASEB Journal · doi:10.1096/fj.202100829rr · Cited by 19 · see citing works
Lactation stage impacts the glycolytic function of bovine CD4+ T cells during ex vivo activation
Eder, J. M., Gorden, P. J., Lippolis, J. D., Reinhardt, T. A., & Sacco, R. E. (2020) · Scientific Reports · doi:10.1038/s41598-020-60691-2 · Cited by 19 · see citing works
Steffen, J. B. M., Haider, F., Sokolov, E. P., Bock, C., & Sokolova, I. M. (2021) · Journal of Experimental Biology · doi:10.1242/jeb.243082 · Cited by 18 · see citing works
Lee, W. E., Genetzakis, E., & Figtree, G. A. (2023) · Antioxidants · doi:10.3390/antiox12071359 · Cited by 18 · see citing works
Does Oxidation of Mitochondrial Cardiolipin Trigger a Chain of Antiapoptotic Reactions?
Mulkidjanian, A. Y., Shalaeva, D. N., Lyamzaev, K. G., & Chernyak, B. V. (2018) · Biochemistry (Moscow) · doi:10.1134/s0006297918100115 · Cited by 18 · see citing works
Sadri, S., Tomar, N., Yang, C., Audi, S. H., Cowley, A. W., & Dash, R. K. (2023) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2023.109690 · Cited by 17 · see citing works
Alcohol hangover effects on brain cortex non-synaptic mitochondria and synaptosomes bioenergetics
Karadayian, A. G., Lombardi, P., Bustamante, J., & Lores‐Arnaiz, S. (2018) · Alcohol · doi:10.1016/j.alcohol.2018.10.010 · Cited by 17 · see citing works
Alterations of multiple alveolar macrophage states in chronic obstructive pulmonary diseasePreprint
Bassler, K. E., Fujii, W., Kapellos, T. S., Horne, A., Reiz, B., Dudkin, E., Luecken, M. D., Reusch, N., Osei-Sarpong, C., Warnat‐Herresthal, S., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.28.121541 · Cited by 16 · see citing works
GPR50 regulates neuronal development as a mitophagy receptor
Liu, J.-C., Zhao, X., Wu, M.-L., Shi, Y., Huang, Z.-P., Fang, L., Zhu, C., Peng, X., Shi, Z.-L., Lan, L.-J., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06978-y · Cited by 16 · see citing works
Stoner, L. R., Higgins, S., & Paterson, C. A. (2023) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00258.2023 · Cited by 16 · see citing works
Serum lactate dehydrogenase level as a possible predictor of treatment preference in psoriasis
Koguchi‐Yoshioka, H., Watanabe, R., Matsumura, Y., Ishitsuka, Y., Inoue, S., Furuta, J., Nakamura, Y., Okiyama, N., Matsuzaka, T., Shimano, H., et al. (2021) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2021.07.007 · Cited by 16 · see citing works
Patil, V., Bohara, R. A., Winter, C. C., Kilcoyne, M., McMahon, S. S., & Pandit, A. S. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14016 · Cited by 14 · see citing works
Development of isoselenazolium chlorides as selective pyruvate kinase isoform M2 inhibitors
Dimitrijevs, P., Makrecka‐Kuka, M., Bogucka, A., Hyvönen, M., Panteļejevs, T., & Arsenyan, P. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115504 · Cited by 14 · see citing works
Meyer, M., Lamont, S. J., & Bobeck, E. A. (2022) · Frontiers in Veterinary Science · doi:10.3389/fvets.2021.815878 · Cited by 14 · see citing works
Yin and Yang of mitochondrial ROS in Drosophila
Towarnicki, S. G., Kok, L. M., & Ballard, J. W. O. (2020) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2020.104022 · Cited by 14 · see citing works
Liu, C. H., Huang, Z. H., Dong, X. Y., Zhang, X. Q., Li, Y. H., Zhao, G., Sun, B. S., & Shen, Y. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/5135893 · Cited by 14 · see citing works
Role of Constitutive STAR in Mitochondrial Structure and Function in MA-10 Leydig Cells
Galano, M., & Papadopoulos, V. (2022) · Endocrinology · doi:10.1210/endocr/bqac091 · Cited by 13 · see citing works
Plaza, A., Antonazzi, M., Blanco‐Urgoiti, J., Olmo, N. D., & Ruiz‐Gayo, M. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900110 · Cited by 12 · see citing works
Functional Consequences of PDK4 Deficiency in Doberman Pinscher Fibroblasts
Bolfer, L., Estrada, A. H., Larkin, C., Conlon, T. J., Lourenço, F., Taggart, K., Suzuki‐Hatano, S., & Pacak, C. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-60879-6 · Cited by 12 · see citing works
Choi, M., & Kang, K. W. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2022.166570 · Cited by 12 · see citing works
Patil, V., O'Connell, E., Quinlan, L., Fearnhead, H., McMahon, S., & Pandit, A. (2020) · iScience · doi:10.1016/j.isci.2021.102182 · Cited by 11 · see citing works
Liu, Y., Horn, A. M. V., Pham, M. T. N., Dinh, B. N. N., Chen, R., Raphael, S. D. R., Paulino, A. J., Thaker, K., Somadder, A., Frost, D. J., et al. (2024) · Applied and Environmental Microbiology · doi:10.1128/aem.02096-23 · Cited by 11 · see citing works
Sadri, S., Zhang, X., Audi, S. H., Cowley, A. W., & Dash, R. K. (2023) · Function · doi:10.1093/function/zqad038 · Cited by 10 · see citing works
Gaafary, M. E., Abdel-Baki, P. M., Halawany, A. M. E., Mohamed, H. M., Duweb, A., Abdallah, H. M., Mohamed, G. A., Ibrahim, S. R. M., Simmet, T., & Syrovets, T. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117365 · Cited by 10 · see citing works
Mitochondrial bioenergetics of breast cancer
Singh, T., Sharma, K., Jena, L., Kaur, P., Singh, S., & Munshi, A. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.101951 · Cited by 11 · see citing works
The impact of obesity on mitochondrial dysfunction during pregnancy
de Oliveira, M. P., da Silva, L. E., Fernandes, B. B., da Silva, M. R., Pistóia, D. G., Cichella, T. D. S., Jacinto, L. B., Spuldaro, K. M., Iser, B. P. M., & Rezin, G. T. (2025) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2025.112463 · Cited by 10 · see citing works
Hebert, J. F., & Myatt, L. (2023) · Antioxidants · doi:10.3390/antiox12030719 · Cited by 10 · see citing works
High rate of hypertension in patients with m.3243A>G MELAS mutations and POLG variants
Pauls, A. D., Sandhu, V., Young, D., Nevay, D., Yeung, D. F., Sirrs, S. M., Tsang, M., Tsang, T. S. M., Lehman, A., Mezei, M. M., et al. (2020) · Mitochondrion · doi:10.1016/j.mito.2020.05.011 · Cited by 10 · see citing works
- Authors
- Cheng, J., Nanayakkara, G., Shao, Y., Cueto, R., Wang, L., Yang, W. Y., Tian, Y., Wang, H., & Yang, X.
- Affiliations
- Harbin Medical University (CN)
- Temple University (US)
- Corresponding author
- Yang, Xiaofeng
- Venue
- Advances in Experimental Medicine and Biology
- Publisher
- Springer International Publishing
- Published
- 2017
- Volume
- 982
- Pages
- 359-370
- ISSN
- 0065-2598 (ISSN-L)
- 2214-8019
- PMC
- PMC5630226
- OpenAlex
- W2617303046
- Cited by
- 168
- References
- 51
- Citations by year
- 2026: 6 · 2025: 22 · 2024: 18 · 2023: 29 · 2022: 25 · 2021: 16 · 2020: 29 · 2019: 8 · 2018: 13 · 2017: 2
- FWCI
- 17.73
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advances in experimental medicine and biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL117654, R01HL138749, R01HL131460, R01HL132399)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK113775, R01DK104116)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- mitochondrial proton leak, uncoupling proteins, uncoupling, reactive oxygen species, electron transport chain, oxidative stress, ischemia-reperfusion injury, UCP2, vascular function, obesity, diabetes mellitus, hypertension, endothelial activation, inflammation, ATP production, cardiovascular disease pathogenesis
- MeSH terms
- Adenosine Triphosphate, Animals, Cardiovascular Diseases, Electron Transport, Energy Metabolism, Humans, Mitochondria, Heart, Protons, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, Myocytes, Cardiac, Electron Transport Chain Complex Proteins, Membrane Potential, Mitochondrial
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