VDAC oligomers form mitochondrial pores to release mtDNA fragments and promote lupus-like disease
Open accessAbstract
VDACs are MOM's ruin: Mitochondrial DNA (mtDNA) is normally kept within the mitochondria. It can be released into the cytosol in response to stress and thus encounter cytosolic DNA sensors, triggering type I interferon responses. During apoptosis, mtDNA release is mediated by macropores in the mitochondrial outer membrane (MOM) created by oligomerization of the proteins BAX and BAK. Kim et al. found that during oxidative stress, mtDNA escapes instead through macropores formed by oligomerization of voltage-dependent anion channels (VDACs) (see the Perspective by Crow). In a mouse model of lupus, an inhibitor of VDAC oligomerization diminished mtDNA release and downstream signaling events. This treatment reduced lupus-like symptoms in the model, suggesting a potential therapeutic route for conditions mediated by mtDNA release. Science , this issue p. 1531 ; see also p. 1445
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In peripheral blood mononuclear cells, the level of VDAC oligomers and cytosolic mitochondrial DNA is higher in patients with SLE than in healthy individuals.
“in peripheral blood mononuclear cells, the level of VDAC oligomers and cytosolic mtDNA is higher in patients with SLE than in healthy individuals”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [148]
The passage discussing Fig. 4B reports more VDAC1 oligomers in PBMCs from patients with SLE than in healthy controls. It reports elevated cytosolic mtDNA in splenocytes from lupus-prone mice, not in human PBMCs; the latter part of the claim is therefore unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCytosolic release of mitochondrial DNA can occur in live cells through VDAC oligomer pores independently of BAX-BAK macropores and can activate the cGAS-STING pathway, as shown in Endog-deficient mouse embryo fibroblasts.
“Cytosolic release of mtDNA can occur in live cells (as opposed to apoptotic cells) via pores formed by VDAC oligomers independent of BAX–BAK macropores and can activate the cGAS–STING pathway, as shown in mouse embryo fibroblasts deficient in Endog (a nuclear DNA-encoded mitochondrial endonuclease)148”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [148]
Splenocytes from lupus-prone mice have more VDAC pores and cytosolic mitochondrial DNA than splenocytes from wild-type mice.
“splenocytes from lupus-prone mice have more VDAC pores and cytosolic mtDNA than splenocytes from wild-type mice”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [148]
Treatment with VBIT-4, a VDAC oligomerization inhibitor, can abrogate SLE-like symptoms in lupus-prone mice and is paralleled by a decrease in cytosolic mitochondrial DNA.
“treatment with VBIT-4, a VDAC oligomerization inhibitor, can abrogate the SLE-like symptoms of lupus-prone mice, which is paralleled by a concomitant decrease in cytosolic mtDNA”
From The role of mitochondria in rheumatic diseases (2022) · cites this paper as [148]
VDAC oligomerization has been proposed to mediate mtDNA release into the cytoplasm.
“Interestingly, a recent study has proposed a role for voltage-dependent anion channel (VDAC) oligomerization in mediating mtDNA release into the cytoplasm (Kim et al., 2019).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Kim et al., 2019
Mouse fibroblasts deficient in mitochondrial endonuclease γ have increased oxidative stress and higher cytosolic mtDNA, which can be attenuated by knocking down VDAC 1 and 3.
“It was shown that mouse fibroblasts deficient in the mitochondrial endonuclease γ, which display increased oxidative stress, had higher levels of cytosolic mtDNA and this could be attenuated by knocking down VDAC 1 and 3 (Kim et al., 2019).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Kim et al., 2019
Cytoplasmic mtDNA accumulating due to mitochondrial endonuclease γ deficiency induces ISG expression in mouse fibroblasts, suggesting cytosolic mtDNA is a major trigger of inflammatory pathways.
“Moreover, cytoplasmic mtDNA that accumulates in response to mitochondrial endonuclease γ deficiency, has also been shown to induce expression of ISGs in mouse fibroblasts (Kim et al., 2019), suggesting that cytosolic mtDNA is a major trigger of inflammatory pathways.”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Kim et al., 2019
Inhibiting VDAC oligomerization with VBIT-4 decreases mtDNA release and IFN signaling in a mouse model of systemic lupus erythematosus and ameliorates disease severity.
“Furthermore, inhibiting VDAC oligomerization by using the inhibitor VBIT-4 has been shown to decrease mtDNA release and IFN signaling in a mouse model of systemic lupus erythematosus and ameliorated the disease severity (Kim et al., 2019), suggesting that inhibition of VDAC oligomerization and perhaps mPTP might represent an effective therapeutic strategy to improve diseases involving cytosolic mt”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Kim et al., 2019
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
RETRACTED ARTICLE: Parkin and PINK1 mitigate STING-induced inflammation
Sliter, D. A., Martinez, J., Hao, L., Chen, X., Sun, N., Fischer, T. D., Burman, J. L., Li, Y., Zhang, Z., Narendra, D. P., et al. (2018) · Nature · doi:10.1038/s41586-018-0448-9 · Cited by 1,287 · see citing works
RetractedHochberg, M. C. (1997) · Arthritis & Rheumatism · doi:10.1002/art.1780400928 · Cited by 11,409 · see citing works
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602 · see citing works
Nakahira, K., Haspel, J. A., Rathinam, V. A. K., Lee, S.-J., Dolinay, T., Lam, H. C., Englert, J. A., Rabinovitch, M., Cernadas, M., Kim, H. P., et al. (2011) · Nature Immunology · doi:10.1038/ni.1980 · Cited by 3,049 · see citing works
SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE ACTIVITY INDEX
Gladman, D. D., Ibañez, D., & Urowitz, M. B. (2007) · Elsevier eBooks · doi:10.1016/b978-0-323-04434-9.50060-9 · Cited by 2,928 · see citing works
Mitochondrial DNA stress primes the antiviral innate immune response
West, A. P., Khoury-Hanold, W., Staron, M., Tal, M. C., Pineda, C. M., Lang, S. M., Bestwick, M., Duguay, B. A., Raimundo, N., MacDuff, D. A., et al. (2015) · Nature · doi:10.1038/nature14156 · Cited by 1,975 · see citing works
Lood, C., Blanco, L. P., Purmalek, M. M., Carmona-Rivera, C., De Ravin, S. S., Smith, C. K., Malech, H. L., Ledbetter, J. A., Elkon, K. B., & Kaplan, M. J. (2016) · Nature Medicine · doi:10.1038/nm.4027 · Cited by 1,570 · see citing works
Self-citationProtein-binding assays in biological liquids using microscale thermophoresis
Wienken, C. J., Baaske, P., Rothbauer, U., Braun, D., & Duhr, S. (2010) · Nature Communications · doi:10.1038/ncomms1093 · Cited by 1,145 · see citing works
Mitochondrial DNA in innate immune responses and inflammatory pathology
West, A. P., & Shadel, G. S. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.21 · Cited by 1,115 · see citing works
BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis
McArthur, K., Whitehead, L. W., Heddleston, J. M., Li, L., Padman, B. S., Oorschot, V., Geoghegan, N. D., Chappaz, S., Davidson, S., San Chin, H., et al. (2018) · Science · doi:10.1126/science.aao6047 · Cited by 1,072 · see citing works
Systemic Lupus Erythematosus Disease Activity Index
National Cancer Institute (2020) · Definitions · doi:10.32388/n5g0vc · Cited by 1,029 · see citing works
Apoptotic Caspases Suppress mtDNA-Induced STING-Mediated Type I IFN Production
White, M. J., McArthur, K., Metcalf, D., Lane, R. M., Cambier, J. C., Herold, M. J., van Delft, M. F., Bedoui, S., Lessene, G., Ritchie, M. E., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.036 · Cited by 983 · see citing works
Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells
Wieckowski, M. R., Giorgi, C., Lebiedzinska, M., Duszynski, J., & Pinton, P. (2009) · Nature Protocols · doi:10.1038/nprot.2009.151 · Cited by 979 · see citing works
Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death
Baines, C. P., Kaiser, R. A., Sheiko, T., Craigen, W. J., & Molkentin, J. D. (2007) · Nature Cell Biology · doi:10.1038/ncb1575 · Cited by 971 · see citing works
VDAC2 Inhibits BAK Activation and Mitochondrial Apoptosis
Cheng, E. H.-Y., Sheiko, T. V., Fisher, J. K., Craigen, W. J., & Korsmeyer, S. J. (2003) · Science · doi:10.1126/science.1083995 · Cited by 852 · see citing works
Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA
Rongvaux, A., Jackson, R., Harman, C. C. D., Li, T., West, A. P., de Zoete, M. R., Wu, Y., Yordy, B., Lakhani, S. A., Kuan, C.-Y., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.037 · Cited by 847 · see citing works
Denny, M. F., Yalavarthi, S., Zhao, W., Thacker, S. G., Anderson, M. R., Sandy, A. R., McCune, W. J., & Kaplan, M. J. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0902199 · Cited by 705 · see citing works
Self-citationMitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis
Riley, J. S., Quarato, G., Cloix, C., Lopez, J., O'Prey, J., Pearson, M., Chapman, J., Sesaki, H., Carlin, L. M., Passos, J. F., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201899238 · Cited by 551 · see citing works
Caielli, S., Athale, S., Domic, B., Murat, E., Chandra, M., Banchereau, R., Baisch, J., Phelps, K., Clayton, S., Gong, M., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151876 · Cited by 501 · see citing works
Ichim, G., Lopez, J., Ahmed, S. U., Muthalagu, N., Giampazolias, E., Delgado, M. E., Haller, M., Riley, J. S., Mason, S. M., Athineos, D., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.01.018 · Cited by 479 · see citing works
The functional organization of mitochondrial genomes in human cells
Iborra, F. J., Kimurâ, H., & Cook, P. R. (2004) · BMC Biology · doi:10.1186/1741-7007-2-9 · Cited by 339 · see citing works
Keinan, N., Tyomkin, D., & Shoshan‐Barmatz, V. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00165-10 · Cited by 269 · see citing works
Self-citationFernández, D., Caza, T. N., Bonilla, E., Li, Q., Banerjee, S. K., Middleton, F. A., Phillips, P. E., Crow, M. K., Oess, S., Müller‐Esterl, W., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803600 · Cited by 259 · see citing works
MICU1 Serves as a Molecular Gatekeeper to Prevent In Vivo Mitochondrial Calcium Overload
Liu, J. C., Liu, J., Holmström, K. M., Menazza, S., Parks, R. J., Fergusson, M. M., Yu, Z., Springer, D., Halsey, C., Liu, C., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.07.011 · Cited by 222 · see citing works
The interferon-α signature of systemic lupus erythematosus
Obermoser, G., & Pascual, V. (2010) · Lupus · doi:10.1177/0961203310371161 · Cited by 220 · see citing works
Mitochondrial permeability transition triggers the release of mtDNA fragments
Patrushev, M., Kasymov, V., Patrusheva, V., Ushakova, T., Gogvadze, V., & Gaziev, A. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4424-1 · Cited by 168 · see citing works
VDAC1 functions in Ca2+ homeostasis and cell life and death in health and disease
Shoshan‐Barmatz, V., Krelin, Y., & Shteinfer‐Kuzmine, A. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.06.007 · Cited by 162 · see citing works
Self-citationBen-Hail, D., Begas-Shvartz, R., Shalev, M., Shteinfer-Kuzmine, A., Gruzman, A., Reina, S., De Pinto, V., & Shoshan-Barmatz, V. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.744284 · Cited by 158 · see citing works
Self-citationEndonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function
McDermott‐Roe, C., Ye, J., Ahmed, R., Sun, X.-M., Serafin, A. M., Ware, J. S., Bottolo, L., Muckett, P. J., Cañas, X., Zhang, J., et al. (2011) · Nature · doi:10.1038/nature10490 · Cited by 157 · see citing works
The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis
Keinan, N., Pahima, H. T., Ben-Hail, D., & Shoshan‐Barmatz, V. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.03.017 · Cited by 116 · see citing works
Self-citationSchäfer, P., Scholz, S., Gimadutdinow, O., Cymerman, I. A., Bujnicki, J. M., Ruiz-Carrillo, A., Pingoud, A. M., & Meiß, G. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.02.069 · Cited by 106 · see citing works
Geula, S., Ben-Hail, D., & Shoshan-Barmatz, V. (2012) · Biochemical Journal · doi:10.1042/bj20112079 · Cited by 105 · see citing works
Self-citationSmall-molecule allosteric inhibitors of BAX
Garner, T. P., Amgalan, D., Reyna, D. E., Li, S., Kitsis, R. N., & Gavathiotis, E. (2019) · Nature Chemical Biology · doi:10.1038/s41589-018-0223-0 · Cited by 104 · see citing works
Garcı́a, N., & Chávez, E. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.08.019 · Cited by 94 · see citing works
VDAC1-interacting anion transport inhibitors inhibit VDAC1 oligomerization and apoptosis
Ben-Hail, D., & Shoshan-Barmatz, V. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.04.002 · Cited by 80 · see citing works
Self-citationWang, K., Goodman, K. N., Li, D. Y., Raffeld, M. A., Chavez, M., & Cohen, J. I. (2015) · Journal of Virology · doi:10.1128/jvi.01845-15 · Cited by 29 · see citing works
Self-citationReconstitution of Purified VDAC1 into a Lipid Bilayer and Recording of Channel ConductancePreprint
Ben-Hail, D., & Shoshan‐Barmatz, V. (2013) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot073148 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309 · see citing works
Mitochondrial dysfunction: mechanisms and advances in therapy
Yao, Z., Li, H., Liao, P., Chen, L., Pan, Y., Zheng, Y., Zhang, C., Liu, D., Zheng, M., & Gao, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01839-8 · Cited by 1,274 · see citing works
cGAS–STING drives ageing-related inflammation and neurodegeneration
Gulen, M. F., Samson, N., Keller, A., Schwabenland, M., Liu, C., Glück, S., Thacker, V. V., Favre, L., Mangeat, B., Kroese, L. J., et al. (2023) · Nature · doi:10.1038/s41586-023-06373-1 · Cited by 1,074 · see citing works
Mitochondrial control of inflammation
Marchi, S., Guilbaud, E., Tait, S. W. G., Yamazaki, T., & Galluzzi, L. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-022-00760-x · Cited by 1,027 · see citing works
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS
Yu, C.-H., Davidson, S., Harapas, C. R., Hilton, J. B., Mlodzianoski, M. J., Laohamonthonkul, P., Louis, C., Low, R. R. J., Moecking, J., De Nardo, D., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.020 · Cited by 1,019 · see citing works
Mitochondrial DNA in inflammation and immunity
Riley, J. S., & Tait, S. W. G. (2020) · EMBO Reports · doi:10.15252/embr.201949799 · Cited by 876 · see citing works
Xian, H., Watari, K., Sanchez-Lopez, E., Offenberger, J., Onyuru, J., Sampath, H., Ying, W., Hoffman, H. M., Shadel, G. S., & Karin, M. (2022) · Immunity · doi:10.1016/j.immuni.2022.06.007 · Cited by 850 · see citing works
Mitochondrial signal transduction
Picard, M. A., & Shirihai, O. S. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.10.008 · Cited by 666 · see citing works
Molecular mechanisms of mitochondrial DNA release and activation of the cGAS-STING pathway
Kim, J., Kim, H., & Chung, J. H. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-00965-7 · Cited by 579 · see citing works
Self-citationDAMPs and DAMP-sensing receptors in inflammation and diseases
Ma, M., Jiang, W., & Zhou, R. (2024) · Immunity · doi:10.1016/j.immuni.2024.03.002 · Cited by 541 · see citing works
The cGAS–STING pathway drives type I IFN immunopathology in COVID-19
Domizio, J. D., Gulen, M. F., Saidoune, F., Thacker, V. V., Yatim, A., Sharma, K., Nass, T., Guenova, E., Schaller, M., Conrad, C., et al. (2022) · Nature · doi:10.1038/s41586-022-04421-w · Cited by 538 · see citing works
Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases
Wigerblad, G., & Kaplan, M. J. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00787-0 · Cited by 519 · see citing works
Self-citationMitochondria at the crossroads of health and disease
Suomalainen, A., & Nunnari, J. M. (2024) · Cell · doi:10.1016/j.cell.2024.04.037 · Cited by 512 · see citing works
The type I interferonopathies: 10 years on
Crow, Y. J., & Stetson, D. B. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-021-00633-9 · Cited by 489 · see citing works
The diversified role of mitochondria in ferroptosis in cancer
Liu, Y., Lu, S.-P., Wu, L., Yang, L., Wang, J., & Wang, J. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06045-y · Cited by 473 · see citing works
Picca, A., Calvani, R., Coelho‐Júnior, H. J., Landi, F., Bernabei, R., & Marzetti, E. (2020) · Antioxidants · doi:10.3390/antiox9080647 · Cited by 456 · see citing works
Pathogenesis of systemic lupus erythematosus: risks, mechanisms and therapeutic targets
Crow, M. K. (2023) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2022-223741 · Cited by 420 · see citing works
Zhu, X., Chen, Z., Shen, W., Huang, G., Sedivy, J. M., Wang, H., & Ju, Z. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00646-9 · Cited by 410 · see citing works
Neutrophil extracellular traps: from physiology to pathology
Hidalgo, A., Libby, P., Soehnlein, O., Aramburu, I. V., Papayannopoulos, V., & Silvestre-Roig, C. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab329 · Cited by 404 · see citing works
Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging
Jiménez‐Loygorri, J. I., Villarejo‐Zori, B., Viedma-Poyatos, Á., Zapata‐Muñoz, J., Benítez‐Fernández, R., Frutos-Lisón, M. D., Tomás-Barberán, F. A., Espı́n, J. C., Área-Gómez, E., Gómez-Durán, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45044-1 · Cited by 381 · see citing works
Oduro, P. K., Zheng, X., Wei, J., Yang, Y., Wang, Y., Zhang, H., Liu, E., Gao, X., Du, M., & Wang, Q. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.05.011 · Cited by 349 · see citing works
Fumarate induces vesicular release of mtDNA to drive innate immunity
Zecchini, V. R., Paupe, V., Herranz-Montoya, I., Janssen, J. J. E., Wortel, I. M. N., Morris, J. L., Ferguson, A., Chowdhury, S. R., Segarra‐Mondejar, M., Costa, A. S. H., et al. (2023) · Nature · doi:10.1038/s41586-023-05770-w · Cited by 336 · see citing works
Mitochondrial DNA Release in Innate Immune Signaling
Newman, L. E., & Shadel, G. S. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104401 · Cited by 331 · see citing works
Signaling by cGAS–STING in Neurodegeneration, Neuroinflammation, and Aging
Paul, B. D., Snyder, S. H., & Bohr, V. A. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.008 · Cited by 324 · see citing works
Activation of innate immune cGAS-STING pathway contributes to Alzheimer’s pathogenesis in 5×FAD mice
Xie, X., Ma, G., Li, X., Zhao, J., Zhao, Z., & Zeng, J. (2023) · Nature Aging · doi:10.1038/s43587-022-00337-2 · Cited by 292 · see citing works
Cytoplasmic DNA: sources, sensing, and role in aging and disease
Miller, K. N., Victorelli, S. G., Salmonowicz, H., Dasgupta, N., Liu, T., Passos, J. F., & Adams, P. D. (2021) · Cell · doi:10.1016/j.cell.2021.09.034 · Cited by 288 · see citing works
Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells
Yao, X., Li, W., Fang, D., Xiao, C., Wu, X. W., Li, M., & Luo, Z. Y. (2021) · Advanced Science · doi:10.1002/advs.202100997 · Cited by 281 · see citing works
Mitochondria and Parkinson’s Disease: Clinical, Molecular, and Translational Aspects
Borsche, M., Pereira, S. L., Klein, C., & Grünewald, A. (2020) · Journal of Parkinson s Disease · doi:10.3233/jpd-201981 · Cited by 276 · see citing works
How location and cellular signaling combine to activate the NLRP3 inflammasome
Akbal, A., Dernst, A., Lovotti, M., Mangan, M., McManus, R. M., & Latz, E. (2022) · Cellular and Molecular Immunology · doi:10.1038/s41423-022-00922-w · Cited by 250 · see citing works
Neutrophil extracellular traps in cancer
Cristinziano, L., Modestino, L., Antonelli, A., Marone, G., Simon, H., Varricchi, G., & Galdiero, M. R. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.07.011 · Cited by 247 · see citing works
Mitochondrial DNA-triggered innate immune response: mechanisms and diseases
Hu, M.-M., & Shu, H. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01086-x · Cited by 247 · see citing works
VDAC1 at the Intersection of Cell Metabolism, Apoptosis, and Diseases
Shoshan‐Barmatz, V., Shteinfer‐Kuzmine, A., & Verma, A. (2020) · Biomolecules · doi:10.3390/biom10111485 · Cited by 232 · see citing works
Self-citationErythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE
Caielli, S., Cardenas, J., de Jesus, A. A., Baisch, J., Walters, L., Blanck, J. P., Balasubramanian, P., Stagnar, C., Ohouo, M., Hong, S., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.021 · Cited by 228 · see citing works
Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling
Lepelley, A., Martin-Niclós, M. J., Bihan, M. L., Marsh, J. A., Uggenti, C., Rice, G., Bondet, V., Duffy, D., Hertzog, J., Rehwinkel, J., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20200600 · Cited by 221 · see citing works
Systemic Lupus Erythematosus Pathogenesis: Interferon and Beyond
Caielli, S., Wan, Z., & Pascual, V. (2023) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101921-042422 · Cited by 221 · see citing works
Zhang, Z., Zhou, H., Ouyang, X., Dong, Y., Sarapultsev, A., Luo, S., & Hu, D. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01252-z · Cited by 216 · see citing works
Barrera, M.-J., Aguilera, S., Castro, I., Carvajal, P., Jara, D., Molina, C., González, S., & González, M.-J. (2021) · Autoimmunity Reviews · doi:10.1016/j.autrev.2021.102867 · Cited by 213 · see citing works
Cell Death and Inflammation: The Role of Mitochondria in Health and Disease
Picca, A., Calvani, R., Coelho‐Júnior, H. J., & Marzetti, E. (2021) · Cells · doi:10.3390/cells10030537 · Cited by 203 · see citing works
Mitochondria as Cellular and Organismal Signaling Hubs
Shen, K., Pender, C. L., Bar‐Ziv, R., Zhang, H., Wickham, K., Willey, E., Durieux, J., Ahmad, Q., & Dillin, A. G. (2022) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-120420-015303 · Cited by 203 · see citing works
Mitochondrial function in development and disease
Rossmann, M. P., Dubois, S. M., Agarwal, S., & Zon, L. I. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.048912 · Cited by 191 · see citing works
Niu, B., Lei, X., Xu, Q., Ju, Y., Xu, D., Mao, L., Li, J., Zheng, Y., Sun, N., Zhang, X., et al. (2021) · Cell Biology and Toxicology · doi:10.1007/s10565-021-09624-x · Cited by 185 · see citing works
Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications
Xie, S., Xu, S., Deng, W., & Tang, Q. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01378-8 · Cited by 185 · see citing works
TFAM is an autophagy receptor that limits inflammation by binding to cytoplasmic mitochondrial DNA
Liu, H., Zhen, C., Xie, J., Luo, Z., Zeng, L., Zhao, G., Lu, S., Zhuang, H., Fan, H., Li, X., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01419-6 · Cited by 185 · see citing works
Pore formation in regulated cell death
Flores‐Romero, H., Ros, U., & García‐Sáez, A. J. (2020) · The EMBO Journal · doi:10.15252/embj.2020105753 · Cited by 183 · see citing works
Trumpff, C., Michelson, J., Lagranha, C. J., Taleon, V., Karan, K. R., Sturm, G., Lindqvist, D., Fernström, J., Moser, D., Kaufman, B. A., et al. (2021) · Mitochondrion · doi:10.1016/j.mito.2021.04.002 · Cited by 181 · see citing works
Cell biology of inflammasome activation
Pandey, A., Shen, C. X., Feng, S., & Man, S. M. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.06.010 · Cited by 179 · see citing works
Baik, S. H., Ramanujan, V. K., Becker, C. A., Fett, S., Underhill, D. M., & Wolf, A. J. (2023) · Science Immunology · doi:10.1126/sciimmunol.ade7652 · Cited by 178 · see citing works
Lai, P., Liu, L., Bancaro, N., Troiani, M., Calì, B., Li, Y., Chen, J., Singh, P. K., Arzola, R. A., Attanasio, G., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.03.005 · Cited by 174 · see citing works
Increased Drp1 promotes autophagy and ESCC progression by mtDNA stress mediated cGAS-STING pathway
Li, Y., Chen, H., Yang, Q., Wan, L., Zhao, J., Wu, Y., Wang, J., Yang, Y., Niu, M., Liu, H., et al. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02262-z · Cited by 170 · see citing works
Cellular pyrimidine imbalance triggers mitochondrial DNA–dependent innate immunity
Sprenger, H., MacVicar, T., Bahat, A., Fiedler, K. U., Hermans, S., Ehrentraut, D., Ried, K., Milenkovic, D., Bonekamp, N. A., Larsson, N., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00385-9 · Cited by 165 · see citing works
Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders
Huang, Y., Liu, B., Sinha, S. C., Amin, S., & Gan, L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00672-x · Cited by 164 · see citing works
Mitochondrial event as an ultimate step in ferroptosis
Oh, S. J., Ikeda, M., Ide, T., Hur, K. Y., & Lee, M. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01199-8 · Cited by 164 · see citing works
Mitochondrial cristae architecture protects against mtDNA release and inflammation
He, B., Yu, H., Liu, S., Wan, H., Fu, S., Liu, S., Yang, J. J., Zhang, Z., Huang, H., Li, Q., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111774 · Cited by 154 · see citing works
Metabolic programs define dysfunctional immune responses in severe COVID-19 patients
Thompson, E. A., Cascino, K., Ordoñez, A. A., Zhou, W., Vaghasia, A. M., Hamacher‐Brady, A., Brady, N. R., Sun, I., Wang, R., Rosenberg, A. Z., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108863 · Cited by 152 · see citing works
Regulation of the cGAS-STING Pathway
Zhang, B., Xu, P., & Ablasser, A. (2025) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101721-032910 · Cited by 153 · see citing works
Organellar homeostasis and innate immune sensing
Harapas, C. R., Idiiatullina, E., Al‐Azab, M., Hrovat-Schaale, K., Reygaerts, T., Steiner, A., Laohamonthonkul, P., Davidson, S., Yu, C., Booty, L. M., et al. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00682-8 · Cited by 151 · see citing works
Lu, T., Zhang, J., Cai, J., Xiao, J., Sui, X. Y., Yuan, X., Li, R., Li, Y., Yao, J., Lv, G., et al. (2022) · Biomaterials · doi:10.1016/j.biomaterials.2022.121486 · Cited by 145 · see citing works
Li, J., Zhao, Y., Gong, S., Wang, M., Liu, X., He, Q., Li, Y., Huang, S., Qiao, H., Tan, X.-R., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36523-y · Cited by 143 · see citing works
Mitochondrial function and gastrointestinal diseases
Haque, P. S., Kapur, N., Barrett, T. A., & Theiss, A. L. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00931-2 · Cited by 142 · see citing works
Newman, L. E., Novak, S. W., Rojas, G. R., Tadepalle, N., Schiavon, C. R., Grotjahn, D. A., Towers, C. G., Tremblay, M., Donnelly, M. P., Ghosh, S., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-023-01343-1 · Cited by 141 · see citing works
Lysosomes drive the piecemeal removal of mitochondrial inner membrane
Prashar, A., Bussi, C., Fearns, A., Capurro, M., Gao, X., Sesaki, H., Gutierrez, M. G., & Jones, N. L. (2024) · Nature · doi:10.1038/s41586-024-07835-w · Cited by 139 · see citing works
A break in mitochondrial endosymbiosis as a basis for inflammatory diseases
Murphy, M. P., & O’Neill, L. A. J. (2024) · Nature · doi:10.1038/s41586-023-06866-z · Cited by 138 · see citing works
Gasdermins mediate cellular release of mitochondrial DNA during pyroptosis and apoptosis
de Torre‐Minguela, C., Gómez, A. I., Couillin, I., & Pelegrı́n, P. (2021) · The FASEB Journal · doi:10.1096/fj.202100085r · Cited by 136 · see citing works
Zhang, Q., Wei, J., Liu, Z., Huang, X., Sun, M., Lai, W., Chen, Z., Wu, J., Chen, Y., Guo, X., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102367 · Cited by 135 · see citing works
Mechanisms of mitochondrial DNA escape and its relationship with different metabolic diseases
Pérez-Treviño, P., Velasquez-Esparza, M. M., & Garcı́a, N. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165761 · Cited by 134 · see citing works
Mitochondrial complex I as a therapeutic target for Alzheimer's disease
Trushina, E. V., Trushin, S., & Hasan, M. F. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.11.003 · Cited by 130 · see citing works
Pan, J., 宁波大学农产品质量安全危害因子与风险防控国家重点实验室, 浙. 宁. 3., Fei, C.-J., Hu, Y., Wu, X., Nie, L., Chen, J., 宁波大学梅山校区海洋学院生物化学与分子生物学实验室, 浙. 宁. 3., & 浙江省海洋生物工程重点实验室, 浙. 宁. 3. (2023) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2022.464 · Cited by 129 · see citing works
Chen, L., Dong, J., Liao, S., Wang, S., Wu, Z., Zuo, M., Liu, B., Yan, C., Chen, Y., He, H., et al. (2022) · Hepatology · doi:10.1002/hep.32471 · Cited by 128 · see citing works
Mitochondrial signalling and homeostasis: from cell biology to neurological disease
Collier, J. J., Oláhová, M., McWilliams, T. G., & Taylor, R. W. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2022.12.001 · Cited by 128 · see citing works
Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease
Tumburu, L., Ghosh-Choudhary, S. K., Seifuddin, F., Barbu, E. A., Yang, S., Ahmad, M. M., Wilkins, L. H. W., Tunc, I., Sivakumar, I., Nichols, J. S., et al. (2021) · Blood · doi:10.1182/blood.2020009063 · Cited by 126 · see citing works
Self-citationMitochondrial pores at the crossroad between cell death and inflammatory signaling
Flores‐Romero, H., Dadsena, S., & García‐Sáez, A. J. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.02.021 · Cited by 125 · see citing works
Mitochondria as a target in cancer treatment
Liu, Y., & Shi, Y. (2020) · MedComm · doi:10.1002/mco2.16 · Cited by 120 · see citing works
Mitochondrial Quality Control and Restraining Innate Immunity
Moehlman, A. T., & Youle, R. J. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-021820-101354 · Cited by 120 · see citing works
Type 2 cytokine signaling in macrophages protects from cellular senescence and organismal aging
Zhou, Z., Yao, J., Wu, D., Huang, X., Wang, Y., Li, X., Lu, Q., & Qiu, Y. (2024) · Immunity · doi:10.1016/j.immuni.2024.01.001 · Cited by 120 · see citing works
Mitochondria as intracellular signaling platforms in health and disease
Tan, J. X., & Finkel, T. (2020) · The Journal of Cell Biology · doi:10.1083/jcb.202002179 · Cited by 119 · see citing works
Verma, A., Pittala, S., Alhozeel, B., Shteinfer‐Kuzmine, A., Ohana, E., Gupta, R., Chung, J. H., & Shoshan‐Barmatz, V. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.06.024 · Cited by 116 · see citing works
Self-citationOxidized mitochondrial DNA induces gasdermin D oligomerization in systemic lupus erythematosus
Miao, N., Wang, Z., Wang, Q., Xie, H., Yang, N., Wang, Y., Wang, J. Q., Kang, H., Bai, W., Wang, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36522-z · Cited by 115 · see citing works
Self-citationSTING, the Endoplasmic Reticulum, and Mitochondria: Is Three a Crowd or a Conversation?
Smith, J. A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.611347 · Cited by 114 · see citing works
Zhao, Y., Liu, B., Xu, L., Yu, S., Fu, J., Wang, J., Yan, X., & Su, J. (2021) · Antioxidants · doi:10.3390/antiox10121917 · Cited by 114 · see citing works
Mitochondrial dysfunction: A promising therapeutic target for liver diseases
Chen, P., Yao, L., Yuan, M., Wang, Z., Zhang, Q., Jiang, Y., & Li, L. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.101115 · Cited by 114 · see citing works
Bryant, J. D., Lei, Y., VanPortfliet, J. J., Winters, A. D., & West, A. P. (2022) · Current Protocols · doi:10.1002/cpz1.372 · Cited by 109 · see citing works
Low‐Density Neutrophils in Systemic Lupus Erythematosus
Tay, S. H., Celhar, T., & Fairhurst, A. (2020) · Arthritis & Rheumatology · doi:10.1002/art.41395 · Cited by 107 · see citing works
Prohibitin 1 regulates mtDNA release and downstream inflammatory responses
Liu, H., Fan, H., He, P., Zhuang, H., Liu, X., Chen, M., Zhong, W., Zhang, Y., Zhen, C., Li, Y., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2022111173 · Cited by 106 · see citing works
Verma, A., Shteinfer‐Kuzmine, A., Kamenetsky, N., Pittala, S., Paul, A., Crystal, E. N., Ouro, A., Caspi, V. C., Pandey, S. K., Monsonego, A., et al. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00329-7 · Cited by 106 · see citing works
Self-citationZhou, H., Dai, Z., Li, J., Wang, J., Zhu, H., Chang, X., & Wang, Y. (2023) · Metabolism · doi:10.1016/j.metabol.2022.155383 · Cited by 105 · see citing works
Quan, S., Fu, X., Cai, H., Ren, Z., Xu, Y., & Jia, L. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00815-2 · Cited by 107 · see citing works
Irazoki, A., Gordaliza‐Alaguero, I., Frank, E., Giakoumakis, N.-N., Seco, J., Palacı́n, M., Gumà, A., Sylow, L., Sebastián, D., & Zorzano, A. (2023) · Nature Communications · doi:10.1038/s41467-022-35732-1 · Cited by 104 · see citing works
Noncanonical Cell Fate Regulation by Bcl-2 Proteins
Chong, S. J. F., Marchi, S., Petroni, G., Kroemer, G., Galluzzi, L., & Pervaiz, S. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2020.03.004 · Cited by 103 · see citing works
Bite of the wolf: innate immune responses propagate autoimmunity in lupus
Gupta, S., & Kaplan, M. J. (2021) · Journal of Clinical Investigation · doi:10.1172/jci144918 · Cited by 102 · see citing works
Self-citationMitochondrial Dysfunction in Cardiovascular Diseases: Potential Targets for Treatment
Yang, J., Guo, Q., Feng, X., Liu, Y., & Zhou, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.841523 · Cited by 102 · see citing works
Zhou, Y., Bastian, I. N., Long, M. D., Dow, M. T., Li, W., Liu, T., Ngu, R. K., Antonucci, L., Huang, J. Y., Phung, Q. T., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025840118 · Cited by 101 · see citing works
The Role of Voltage-Dependent Anion Channel in Mitochondrial Dysfunction and Human Disease
Varughese, J. T., Buchanan, S. K., & Pitt, A. S. (2021) · Cells · doi:10.3390/cells10071737 · Cited by 101 · see citing works
Liu, Y., Zhang, H., Liu, Y., Zhang, S., Su, P., Wang, L., Li, Y., Liang, Y., Wang, X., Zhao, W., et al. (2023) · Autophagy · doi:10.1080/15548627.2023.2182482 · Cited by 100 · see citing works
Self-citationRed Blood Cell Metabolism In Vivo and In Vitro
D’Alessandro, A., Anastasiadi, A. T., Tzounakas, V. L., Nemkov, T. G., Reisz, J. A., Kriebardis, A. G., Zimring, J. C., Spitalnik, S. L., & Busch, M. P. (2023) · Metabolites · doi:10.3390/metabo13070793 · Cited by 100 · see citing works
Wang, K., Du, Y., Li, P., Guan, C., Zhou, M., Wu, L., Liu, Z., & Huang, Z. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02375-x · Cited by 98 · see citing works
Self-citationMatsui, H., Itô, J., Matsui, N., Uechi, T., Onodera, O., & Kakita, A. (2021) · Nature Communications · doi:10.1038/s41467-021-23452-x · Cited by 97 · see citing works
Hu, H., Guo, L., Overholser, J. P., & Wang, X. (2022) · Cells · doi:10.3390/cells11193174 · Cited by 97 · see citing works
Self-citationBussi, C., Heunis, T. D. J., Pellegrino, E., Bernard, E. M., Bah, N. K., dos Santos, M. S., Santucci, P., Aylan, B., Rodgers, A., Fearns, A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34632-8 · Cited by 96 · see citing works
Oxidized mitochondrial DNA: a protective signal gone awry
Xian, H., & Karin, M. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.01.006 · Cited by 94 · see citing works
You, Y.-P., Liang, Y., Ke, H.-Y., Li, Y., Shi, Z., Zhou, Z.-Y., Yang, H., Yuan, T., Gan, Y.-Q., Lu, N., et al. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01376-8 · Cited by 94 · see citing works
- Authors
- Kim, J., Gupta, R., Blanco, L. P., Yang, S., Shteinfer-Kuzmine, A., Wang, K., Zhu, J., Yoon, H. E., Wang, X., Kerkhofs, M., Kang, H., Brown, A. L., Park, S.-J., Xu, X., Zandee van Rilland, E., Kim, M. K., Cohen, J. I., Kaplan, M. J., Shoshan-Barmatz, V., & Chung, J. H.
- Affiliations
- National Heart, Lung, and Blood Institute (US)
- Ben-Gurion University of the Negev (IL)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (US)
- Department of Life Sciences and National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
- National Institutes of Health (US)
- Mokobio Biotechnology R&D Center, Rockville, MD 20850, USA.
- Laboratory of Obesity and Aging Research, Cardiovascular Branch, National Heart Lung and Blood Institute, Bethesda, MD 20892, USA.
- Corresponding author
- Chung, Jay H.
- ORCID
- Venue
- Science
- Published
- 2019-12-20
- Volume
- 366
- Issue
- 6472
- Pages
- 1531-1536
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC8325171
- OpenAlex
- W2996537134
- Cited by
- 793
- References
- 37
- Citations by year
- 2026: 172 · 2025: 147 · 2024: 147 · 2023: 123 · 2022: 82 · 2021: 86 · 2020: 35 · 2019: 1
- FWCI
- 16.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Funders
- National Institutes of Health
- Korea Health Industry Development Institute (HI14C1176)
- Korea Research Institute of Bioscience and Biotechnology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- VDAC1, mitochondrial DNA release, mitochondrial outer membrane permeabilization, mitochondrial stress, type I interferon signaling, systemic lupus erythematosus, neutrophil extracellular traps, N-terminal domain
- MeSH terms
- Protein Domains, Animals, Disease Models, Animal, DNA, Mitochondrial, Endodeoxyribonucleases, Humans, Interferons, Lupus Erythematosus, Systemic, Oxidative Stress, Voltage-Dependent Anion Channels, Mitochondrial Membranes, Mice, Rats, Protein Multimerization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review