Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis

Saul Soberanes; Alexander V. Misharin; Amit Jairaman; Luisa Morales-Nebreda; Alexandra C. McQuattie-Pimentel; Takugo Cho; Robert B. Hamanaka; Angelo Y. Meliton; Paul A. Reyfman; James M. Walter; Ching I. Chen; Monica Chi; Stephen Chiu; Francisco J. Gonzalez-Gonzalez; Matthew Antalek; Hiam Abdala-Valencia; Sergio E. Chiarella; Kaitlyn A. Sun; Parker S. Woods; Andrew J. Ghio; Manu Jain; Harris Perlman; Karen M. Ridge; Richard I. Morimoto; Jacob I. Sznajder; William E. Balch; Sangeeta M. Bhorade; Ankit Bharat; Murali Prakriya; Navdeep S. Chandel; Gökhan M. Mutlu; G. R.Scott Budinger

doi:10.1016/j.cmet.2018.09.019

Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis

Saul Soberanes, Alexander V. Misharin, Amit Jairaman, Luisa Morales-Nebreda, Alexandra C. McQuattie-Pimentel, Takugo Cho, Robert B. Hamanaka, Angelo Y. Meliton, Paul A. Reyfman, James M. Walter, Ching I. Chen, Monica Chi, Stephen Chiu, Francisco J. Gonzalez-Gonzalez, Matthew Antalek, Hiam Abdala-Valencia, Sergio E. Chiarella, Kaitlyn A. Sun, Parker S. Woods, Andrew J. GhioManu Jain, Harris Perlman, Karen M. Ridge, Richard I. Morimoto, Jacob I. Sznajder, William E. Balch, Sangeeta M. Bhorade, Ankit Bharat, Murali Prakriya, Navdeep S. Chandel, Gökhan M. Mutlu^*, G. R.Scott Budinger

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

Abstract

Air pollution exposure has been linked to a variety of poor health outcomes, including an increased risk of death attributable to ischemic cardiovascular events. Soberanes et al. find that metformin may hold promise as a therapy, as its capacity to act as a mitochondrial complex I inhibitor prevents accelerated thrombosis in a murine model of particulate-matter inhalation.

Original language	English (US)
Pages (from-to)	335-347.e5
Journal	Cell Metabolism
Volume	29
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2018.09.019
State	Published - Feb 5 2019

Funding

A.V.M.: NHLBI HL135124 , NIH NIAMS AR061593 , ATS/Scleroderma Foundation Research Grant , DOD grant PR141319 , and BD Bioscience Immunology Research Grant . P.A.R.: HL076139 . A.B.: NIH HL125940 and the Thoracic Surgery Foundation , Society of University Surgeons , John H. Gibbon Jr. Research Scholarship from American Association of Thoracic Surgery. B.D.J.: HL128867 , Parker B. Francis Research Opportunity Award. J.I.S.: NIH AG049665 , HL048129 , HL071643 , HL085534 . G.M.M.: NIH ES015024 and ES025644 and ES026718 . K.R.: NIH HL079190 and HL124664 . G.R.S.B.: NIH ES013995 , HL071643 , AG049665 , VA BX000201 , DOD PR141319 . H.P.: NIH AR064546 , AG049665 HL134375 and the Mabel Greene Myers Chair. N.S.C.: NIH grants AG049665 , HL071643 , CA197532 . Core Facilities (Flow Cytometry and Genomics NCI Cancer Center Support Grant P30 CA060553 ), the Feinberg School of Medicine, the Center for Genetic Medicine , and Feinberg's Department of Biochemistry and Molecular Genetics , the Office of the Provost , the Office for Research , and Northwestern Information Technology , and maintained and developed by Feinberg IT and Research Computing Group. A.V.M.: NHLBI HL135124, NIH NIAMS AR061593, ATS/Scleroderma Foundation Research Grant, DOD grant PR141319, and BD Bioscience Immunology Research Grant. P.A.R.: HL076139. A.B.: NIH HL125940 and the Thoracic Surgery Foundation, Society of University Surgeons, John H. Gibbon Jr. Research Scholarship from American Association of Thoracic Surgery. B.D.J.: HL128867, Parker B. Francis Research Opportunity Award. J.I.S.: NIH AG049665, HL048129, HL071643, HL085534. G.M.M.: NIH ES015024 and ES025644 and ES026718. K.R.: NIH HL079190 and HL124664. G.R.S.B.: NIH ES013995, HL071643, AG049665, VA BX000201, DOD PR141319. H.P.: NIH AR064546, AG049665 HL134375 and the Mabel Greene Myers Chair. N.S.C.: NIH grants AG049665, HL071643, CA197532. Core Facilities (Flow Cytometry and Genomics NCI Cancer Center Support Grant P30 CA060553), the Feinberg School of Medicine, the Center for Genetic Medicine, and Feinberg's Department of Biochemistry and Molecular Genetics, the Office of the Provost, the Office for Research, and Northwestern Information Technology, and maintained and developed by Feinberg IT and Research Computing Group.

Keywords

air pollution
calcium channels
electron transport chain
mitochondria
proteostasis
reactive oxygen species
signaling
thrombosis

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2018.09.019

Cite this

Soberanes, S., Misharin, A. V., Jairaman, A., Morales-Nebreda, L., McQuattie-Pimentel, A. C., Cho, T., Hamanaka, R. B., Meliton, A. Y., Reyfman, P. A., Walter, J. M., Chen, C. I., Chi, M., Chiu, S., Gonzalez-Gonzalez, F. J., Antalek, M., Abdala-Valencia, H., Chiarella, S. E., Sun, K. A., Woods, P. S., ... Budinger, G. R. S. (2019). Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis. Cell Metabolism, 29(2), 335-347.e5. https://doi.org/10.1016/j.cmet.2018.09.019

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title = "Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis",

abstract = "Air pollution exposure has been linked to a variety of poor health outcomes, including an increased risk of death attributable to ischemic cardiovascular events. Soberanes et al. find that metformin may hold promise as a therapy, as its capacity to act as a mitochondrial complex I inhibitor prevents accelerated thrombosis in a murine model of particulate-matter inhalation.",

keywords = "air pollution, calcium channels, electron transport chain, mitochondria, proteostasis, reactive oxygen species, signaling, thrombosis",

author = "Saul Soberanes and Misharin, {Alexander V.} and Amit Jairaman and Luisa Morales-Nebreda and McQuattie-Pimentel, {Alexandra C.} and Takugo Cho and Hamanaka, {Robert B.} and Meliton, {Angelo Y.} and Reyfman, {Paul A.} and Walter, {James M.} and Chen, {Ching I.} and Monica Chi and Stephen Chiu and Gonzalez-Gonzalez, {Francisco J.} and Matthew Antalek and Hiam Abdala-Valencia and Chiarella, {Sergio E.} and Sun, {Kaitlyn A.} and Woods, {Parker S.} and Ghio, {Andrew J.} and Manu Jain and Harris Perlman and Ridge, {Karen M.} and Morimoto, {Richard I.} and Sznajder, {Jacob I.} and Balch, {William E.} and Bhorade, {Sangeeta M.} and Ankit Bharat and Murali Prakriya and Chandel, {Navdeep S.} and Mutlu, {G{\"o}khan M.} and Budinger, {G. R.Scott}",

note = "Funding Information: A.V.M.: NHLBI HL135124 , NIH NIAMS AR061593 , ATS/Scleroderma Foundation Research Grant , DOD grant PR141319 , and BD Bioscience Immunology Research Grant . P.A.R.: HL076139 . A.B.: NIH HL125940 and the Thoracic Surgery Foundation , Society of University Surgeons , John H. Gibbon Jr. Research Scholarship from American Association of Thoracic Surgery. B.D.J.: HL128867 , Parker B. Francis Research Opportunity Award. J.I.S.: NIH AG049665 , HL048129 , HL071643 , HL085534 . G.M.M.: NIH ES015024 and ES025644 and ES026718 . K.R.: NIH HL079190 and HL124664 . G.R.S.B.: NIH ES013995 , HL071643 , AG049665 , VA BX000201 , DOD PR141319 . H.P.: NIH AR064546 , AG049665 HL134375 and the Mabel Greene Myers Chair. N.S.C.: NIH grants AG049665 , HL071643 , CA197532 . Core Facilities (Flow Cytometry and Genomics NCI Cancer Center Support Grant P30 CA060553 ), the Feinberg School of Medicine, the Center for Genetic Medicine , and Feinberg's Department of Biochemistry and Molecular Genetics , the Office of the Provost , the Office for Research , and Northwestern Information Technology , and maintained and developed by Feinberg IT and Research Computing Group. Funding Information: A.V.M.: NHLBI HL135124, NIH NIAMS AR061593, ATS/Scleroderma Foundation Research Grant, DOD grant PR141319, and BD Bioscience Immunology Research Grant. P.A.R.: HL076139. A.B.: NIH HL125940 and the Thoracic Surgery Foundation, Society of University Surgeons, John H. Gibbon Jr. Research Scholarship from American Association of Thoracic Surgery. B.D.J.: HL128867, Parker B. Francis Research Opportunity Award. J.I.S.: NIH AG049665, HL048129, HL071643, HL085534. G.M.M.: NIH ES015024 and ES025644 and ES026718. K.R.: NIH HL079190 and HL124664. G.R.S.B.: NIH ES013995, HL071643, AG049665, VA BX000201, DOD PR141319. H.P.: NIH AR064546, AG049665 HL134375 and the Mabel Greene Myers Chair. N.S.C.: NIH grants AG049665, HL071643, CA197532. Core Facilities (Flow Cytometry and Genomics NCI Cancer Center Support Grant P30 CA060553), the Feinberg School of Medicine, the Center for Genetic Medicine, and Feinberg's Department of Biochemistry and Molecular Genetics, the Office of the Provost, the Office for Research, and Northwestern Information Technology, and maintained and developed by Feinberg IT and Research Computing Group. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2019",

month = feb,

day = "5",

doi = "10.1016/j.cmet.2018.09.019",

language = "English (US)",

volume = "29",

pages = "335--347.e5",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "2",

}

Soberanes, S, Misharin, AV, Jairaman, A, Morales-Nebreda, L, McQuattie-Pimentel, AC, Cho, T, Hamanaka, RB, Meliton, AY, Reyfman, PA, Walter, JM, Chen, CI, Chi, M, Chiu, S, Gonzalez-Gonzalez, FJ, Antalek, M, Abdala-Valencia, H, Chiarella, SE, Sun, KA, Woods, PS, Ghio, AJ, Jain, M , Perlman, H , Ridge, KM , Morimoto, RI , Sznajder, JI, Balch, WE, Bhorade, SM, Bharat, A , Prakriya, M , Chandel, NS, Mutlu, GM & Budinger, GRS 2019, 'Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis', Cell Metabolism, vol. 29, no. 2, pp. 335-347.e5. https://doi.org/10.1016/j.cmet.2018.09.019

TY - JOUR

T1 - Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis

AU - Soberanes, Saul

AU - Misharin, Alexander V.

AU - Jairaman, Amit

AU - Morales-Nebreda, Luisa

AU - McQuattie-Pimentel, Alexandra C.

AU - Cho, Takugo

AU - Hamanaka, Robert B.

AU - Meliton, Angelo Y.

AU - Reyfman, Paul A.

AU - Walter, James M.

AU - Chen, Ching I.

AU - Chi, Monica

AU - Chiu, Stephen

AU - Gonzalez-Gonzalez, Francisco J.

AU - Antalek, Matthew

AU - Abdala-Valencia, Hiam

AU - Chiarella, Sergio E.

AU - Sun, Kaitlyn A.

AU - Woods, Parker S.

AU - Ghio, Andrew J.

AU - Jain, Manu

AU - Perlman, Harris

AU - Ridge, Karen M.

AU - Morimoto, Richard I.

AU - Sznajder, Jacob I.

AU - Balch, William E.

AU - Bhorade, Sangeeta M.

AU - Bharat, Ankit

AU - Prakriya, Murali

AU - Chandel, Navdeep S.

AU - Mutlu, Gökhan M.

AU - Budinger, G. R.Scott

N1 - Funding Information: A.V.M.: NHLBI HL135124 , NIH NIAMS AR061593 , ATS/Scleroderma Foundation Research Grant , DOD grant PR141319 , and BD Bioscience Immunology Research Grant . P.A.R.: HL076139 . A.B.: NIH HL125940 and the Thoracic Surgery Foundation , Society of University Surgeons , John H. Gibbon Jr. Research Scholarship from American Association of Thoracic Surgery. B.D.J.: HL128867 , Parker B. Francis Research Opportunity Award. J.I.S.: NIH AG049665 , HL048129 , HL071643 , HL085534 . G.M.M.: NIH ES015024 and ES025644 and ES026718 . K.R.: NIH HL079190 and HL124664 . G.R.S.B.: NIH ES013995 , HL071643 , AG049665 , VA BX000201 , DOD PR141319 . H.P.: NIH AR064546 , AG049665 HL134375 and the Mabel Greene Myers Chair. N.S.C.: NIH grants AG049665 , HL071643 , CA197532 . Core Facilities (Flow Cytometry and Genomics NCI Cancer Center Support Grant P30 CA060553 ), the Feinberg School of Medicine, the Center for Genetic Medicine , and Feinberg's Department of Biochemistry and Molecular Genetics , the Office of the Provost , the Office for Research , and Northwestern Information Technology , and maintained and developed by Feinberg IT and Research Computing Group. Funding Information: A.V.M.: NHLBI HL135124, NIH NIAMS AR061593, ATS/Scleroderma Foundation Research Grant, DOD grant PR141319, and BD Bioscience Immunology Research Grant. P.A.R.: HL076139. A.B.: NIH HL125940 and the Thoracic Surgery Foundation, Society of University Surgeons, John H. Gibbon Jr. Research Scholarship from American Association of Thoracic Surgery. B.D.J.: HL128867, Parker B. Francis Research Opportunity Award. J.I.S.: NIH AG049665, HL048129, HL071643, HL085534. G.M.M.: NIH ES015024 and ES025644 and ES026718. K.R.: NIH HL079190 and HL124664. G.R.S.B.: NIH ES013995, HL071643, AG049665, VA BX000201, DOD PR141319. H.P.: NIH AR064546, AG049665 HL134375 and the Mabel Greene Myers Chair. N.S.C.: NIH grants AG049665, HL071643, CA197532. Core Facilities (Flow Cytometry and Genomics NCI Cancer Center Support Grant P30 CA060553), the Feinberg School of Medicine, the Center for Genetic Medicine, and Feinberg's Department of Biochemistry and Molecular Genetics, the Office of the Provost, the Office for Research, and Northwestern Information Technology, and maintained and developed by Feinberg IT and Research Computing Group. Publisher Copyright: © 2018 Elsevier Inc.

PY - 2019/2/5

Y1 - 2019/2/5

N2 - Air pollution exposure has been linked to a variety of poor health outcomes, including an increased risk of death attributable to ischemic cardiovascular events. Soberanes et al. find that metformin may hold promise as a therapy, as its capacity to act as a mitochondrial complex I inhibitor prevents accelerated thrombosis in a murine model of particulate-matter inhalation.

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KW - air pollution

KW - calcium channels

KW - electron transport chain

KW - mitochondria

KW - proteostasis

KW - reactive oxygen species

KW - signaling

KW - thrombosis

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Metformin Targets Mitochondrial Electron Transport to Reduce Air-Pollution-Induced Thrombosis

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