{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:06:33Z","timestamp":1790514393116,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T00:00:00Z","timestamp":1617321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY026012"],"award-info":[{"award-number":["R01EY026012"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EY0285541"],"award-info":[{"award-number":["R01EY0285541"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30EY11374"],"award-info":[{"award-number":["P30EY11374"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016944","name":"Regenerative Medicine Minnesota","doi-asserted-by":"publisher","award":["2015-5337, 091717 TR 009"],"award-info":[{"award-number":["2015-5337, 091717 TR 009"]}],"id":[{"id":"10.13039\/100016944","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, is characterized by loss of the retinal pigment epithelium (RPE). While the disease mechanism remains unclear, prior studies have linked AMD with RPE mitochondrial defects and genetic polymorphisms in the complement pathway. This study used RPE generated from induced pluripotent stem cells (iPSC-RPE), which were derived from human donors with or without AMD and genotyped for the complement factor H (CFH) AMD high-risk allele (rs1061170, Y402H) to investigate whether donor disease state or genotype had a detrimental effect on mitochondrial function and inflammation. Results show that cells derived from donors with AMD display decreased mitochondrial function under conditions of stress and elevated expression of inflammatory markers compared to iPSC-RPE from individuals without AMD. A more pronounced reduction in mitochondrial function and increased inflammatory markers was observed in CFH high-risk cells, irrespective of disease state. These results provide evidence for a previously unrecognized link between CFH and mitochondrial function that could contribute to RPE loss in AMD patients harboring the CFH high-risk genotype.<\/jats:p>","DOI":"10.3390\/cells10040789","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T04:13:51Z","timestamp":1617336831000},"page":"789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"10","author":[{"given":"Mara C.","family":"Ebeling","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Geng","sequence":"additional","affiliation":[{"name":"Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Kapphahn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2232-9494","authenticated-orcid":false,"given":"Heidi","family":"Roehrich","sequence":"additional","affiliation":[{"name":"Histology Core for Vision Research, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3731-8082","authenticated-orcid":false,"given":"Sandra R.","family":"Montezuma","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5074-2614","authenticated-orcid":false,"given":"James R.","family":"Dutton","sequence":"additional","affiliation":[{"name":"Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Ferrington","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1001\/archopht.122.4.564","article-title":"Prevalence of age-related macular degeneration in the United States","volume":"122","author":"Friedman","year":"2004","journal-title":"Arch. Ophthalomol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"563","DOI":"10.2147\/OPTH.S59724","article-title":"Recent developments in the management of dry age-related macular degeneration","volume":"9","author":"Buschini","year":"2015","journal-title":"Clin. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","article-title":"A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants","volume":"48","author":"Fritsche","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1001\/archopht.125.1.55","article-title":"A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors","volume":"125","author":"Shaumberg","year":"2007","journal-title":"Arch. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1016\/j.molimm.2010.05.007","article-title":"Complement control protein factor H: The good, the bad, and the inadequate","volume":"47","author":"Ferreira","year":"2010","journal-title":"Mol. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.preteyeres.2009.11.003","article-title":"The pivotal role of the complement system in aging and age-related macular degeneration: Hypothesis revisited","volume":"29","author":"Anderson","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30192","DOI":"10.1074\/jbc.M110.103986","article-title":"Impaired binding of age-related macular degeneration-associated complement factor H 402H allotype to Brich\u2019s membrane in human retina","volume":"285","author":"Clark","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1093\/ije\/dyr204","article-title":"Complement Factor H genetic variant and age-related macular degeneration: Effect size, modifiers and relationship to disease subtype","volume":"41","author":"Sofat","year":"2012","journal-title":"Int. J. Epidemiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.molimm.2016.11.016","article-title":"The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment","volume":"84","author":"Geerlings","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1152\/physrev.00021.2004","article-title":"The retinal pigment epithelium in visual function","volume":"85","author":"Strauss","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.neurobiolaging.2005.05.012","article-title":"Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration","volume":"27","author":"Feher","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1167\/iovs.07-1352","article-title":"Mitochondrial proteomics of the retinal pigment epithelium at progressive stages of AMD","volume":"49","author":"Nordgaard","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5470","DOI":"10.1167\/iovs.10-5429","article-title":"Mitochondrial DNA damage as a potential mechanism for age-related macular degeneration","volume":"51","author":"Karunadhrama","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7304","DOI":"10.1523\/JNEUROSCI.0190-15.2015","article-title":"Investigating mitochondria as a target for treating age-related macular degeneration","volume":"35","author":"Terluk","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_15","first-page":"3251","article-title":"Mitochondrial DNA damage and repair in RPE associated with aging and age-related macular degeneration","volume":"52","author":"Lin","year":"2011","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.redox.2017.05.015","article-title":"Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration","volume":"13","author":"Ferrington","year":"2017","journal-title":"Redox Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.exer.2016.01.018","article-title":"Increased retinal mtDNA damage in the CFH variant associated with age-related macular degeneration","volume":"145","author":"Ferrington","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e28899","DOI":"10.7554\/eLife.28899","article-title":"Biochemical adaptations of the retina and retinal pigment epithelium support a metabolic ecosystem in the vertebrate eye","volume":"6","author":"Kanow","year":"2017","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"AMD41","DOI":"10.1167\/iovs.18-24289","article-title":"Perspective on AMD pathobiology: A bioenergetic crisis in the RPE","volume":"59","author":"Fisher","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kaarniranta, K., Uusitalo, H., Blasiak, J., Felszeghy, S., Kannan, R., Kauppinen, A., Salminen, A., Sinha, D., and Ferrington, D.A. (2020). Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration. Prog. Retin. Eye Res.","DOI":"10.1016\/j.preteyeres.2020.100858"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1186\/s12967-016-1101-8","article-title":"Repressed SIRT1\/PGC-1\u03b1 pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration","volume":"14","author":"Golestaneh","year":"2016","journal-title":"J. Trans. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fields, M.A., Bowrey, H.E., Gong, J., Moreira, E.F., Cai, H., and Del Priore, L.V. (2017). Extracellular matrix nitration alters growth factor release and activates bioactive complement in human retinal pigment epithelial cells. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0177763"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1002\/sctm.19-0321","article-title":"Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions","volume":"9","author":"Gong","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1093\/hmg\/ddu053","article-title":"Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines","volume":"23","author":"Yang","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.stem.2016.12.015","article-title":"Nicotinamide ameliorates disease phenotypes in a human iPSC model of age-related macular degeneration","volume":"20","author":"Saini","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1002\/stem.2708","article-title":"An induced pluripotent stem cell patient specific model of complement factor H (Y402H) polymorphism displays characteristic features of age-related macular degeneration and indicates a beneficial role for UV light exposure","volume":"35","author":"Hallam","year":"2017","journal-title":"Stem Cells"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1002\/sctm.20-0211","article-title":"Complement modulation reverses pathology in Y402H-retinal pigment epithelium cell model of age-related macular degeneration by restoring lysosomal function","volume":"9","author":"Cerniauskas","year":"2020","journal-title":"Stem Cells Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4484","DOI":"10.1167\/iovs.04-0342","article-title":"The Minnesota Grading System of eye bank eyes for age-related macular degeneration","volume":"45","author":"Olson","year":"2004","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Geng, Z., Walsh, P.J., Troung, V., Hill, C., Ebeling, M., Kapphahn, R.J., Montezuma, S.R., Yuan, C., Roehrich, H., and Ferrington, D.A. (2017). Generation of retinal pigmented epithelium from iPSCs derived from conjunctiva of donors with and without age related macular degeneration. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173575"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5174957","DOI":"10.1155\/2019\/5174957","article-title":"N-Acetyl-L-cysteine protects human retinal pigment epithelial cells from oxidative damage: Implications for age-related macular degeneration","volume":"2019","author":"Terluk","year":"2019","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1042\/CS20140101","article-title":"The Bioenergetic Health Index: A new concept in mitochondrial translational research","volume":"127","author":"Chacko","year":"2014","journal-title":"Clin. Sci. (Lond)"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12758","DOI":"10.1073\/pnas.220402097","article-title":"Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium","volume":"97","author":"Marmorstein","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"604","DOI":"10.3389\/fimmu.2016.00604","article-title":"Hall of Fame among Pro-inflammatory cytokines: Interleukin-6 gene and its transcriptional regulation mechanisms","volume":"7","author":"Luo","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bent, R., Moll, L., Grabbe, S., and Bros, M. (2018). Interleukin-1 Beta\u2014A friend or foe in malignancies?. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082155"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"jcs234781","DOI":"10.1242\/jcs.234781","article-title":"Membrane trafficking as an active regulator of constitutively secreted cytokines","volume":"133","author":"Revelo","year":"2020","journal-title":"J. Cell Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101552","DOI":"10.1016\/j.redox.2020.101552","article-title":"Improving retinal mitochondrial function as treatment for age-related macular degeneration","volume":"34","author":"Ebeling","year":"2020","journal-title":"Redox Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e2537","DOI":"10.1038\/cddis.2016.453","article-title":"Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration","volume":"8","author":"Golestaneh","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.5966\/sctm.2016-0037","article-title":"In pursuit of authenticity: Induced pluripotent stem cell-derived retinal pigment epithelium for clinical applications","volume":"11","author":"Miyagishima","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3389\/fnagi.2014.00191","article-title":"The generation of induced pluripotent stem cells for macular degeneration as a drug screening platform: Identification of curcumin as a protective agent for retinal pigment epithelial cells against oxidative stress","volume":"6","author":"Chang","year":"2014","journal-title":"Front. Aging Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1016\/j.neurobiolaging.2015.06.010","article-title":"Mitochondrial decline precedes phenotype development in the complement factor H mouse model of retinal degeneration but can be corrected by near infrared light","volume":"36","author":"Calaza","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10320","DOI":"10.1038\/s41598-020-67292-z","article-title":"Loss of complement factor H impairs antioxidant capacity and energy metabolism of human RPE cells","volume":"10","author":"Armento","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1038\/s41598-018-37673-6","article-title":"Complement factor H regulates retinal development and its absence may establish a footprint for age related macular degeneration","volume":"9","author":"Sivapathasuntharam","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"16651","DOI":"10.1073\/pnas.0705079104","article-title":"Complement factor H deficiency in aged mice causes retinal abnormalities and visual dysfunction","volume":"104","author":"Coffey","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1073\/pnas.1814014116","article-title":"Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice","volume":"116","author":"Landowski","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.smim.2018.03.003","article-title":"Intracellular complement activation\u2014An alarm raising mechanism?","volume":"38","author":"Reichhardt","year":"2018","journal-title":"Semin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00281-017-0649-6","article-title":"The eye as a complement dysregulation hotspot","volume":"40","author":"Clark","year":"2018","journal-title":"Semin. Immunopathol."},{"key":"ref_47","first-page":"1588","article-title":"Complement gene expression and regulation in mouse retina and retinal pigment epithelium\/choroid","volume":"17","author":"Luo","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9014","DOI":"10.1073\/pnas.1805039115","article-title":"Aberrant early endosome biogenesis mediates complement activation in the retinal pigment epithelium in models of macular degeneration","volume":"115","author":"Kaur","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/cdd.2015.164","article-title":"Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes","volume":"23","author":"Martin","year":"2016","journal-title":"Cell Death Diff."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6489","DOI":"10.1167\/iovs.13-12374","article-title":"Complement Factor C3a alters proteasome function in human RPE cells and in an animal model of age-related RPE degeneration","volume":"54","author":"Klassen","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"13873","DOI":"10.1038\/s41598-019-50420-9","article-title":"CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex","volume":"9","author":"Borras","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1074\/jbc.M109.045427","article-title":"Annexin-II, DNA, and histones serve as factor H ligands on the surface of apoptotic cells","volume":"285","author":"Leffler","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.immuni.2013.10.018","article-title":"Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation","volume":"39","author":"Liszewski","year":"2013","journal-title":"Immunity"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2017.00001","article-title":"Keeping it all going\u2014Complement meets metabolism","volume":"8","author":"Kolev","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1002\/eji.201546131","article-title":"A novel \u201ccomplement-metabolism-inflammasome axis\u201d as a key regulator of immune cell effector function","volume":"46","author":"Arbore","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1136\/bjophthalmol-2015-307213","article-title":"CFH Y402H polymorphism and the complement activation product C5a: Effects on NF-\u03baB activation and inflammasome gene regulation","volume":"100","author":"Cao","year":"2016","journal-title":"Br. J. Ophthamol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.immuni.2016.08.003","article-title":"Complement-mediated regulation of metabolism and basic cellular processes","volume":"45","author":"Hess","year":"2016","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/ni.1980","article-title":"Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome","volume":"12","author":"Nakahira","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.immuni.2012.01.009","article-title":"Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis","volume":"36","author":"Shimada","year":"2012","journal-title":"Immunity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating mitochondrial DAMPs cause inflammatory responses to injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Samanta, A., Aziz, A.A., Jhingan, M., Singh, S.R., Khanani, A.M., and Chhablani, J. (2021). Emerging Therapies in Nonexudative Age-Related Macular Degeneration in 2020. Asia Pac. J. Ophthalmol. (Phila).","DOI":"10.1097\/APO.0000000000000355"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/4\/789\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:33:36Z","timestamp":1760362416000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/4\/789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,2]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["cells10040789"],"URL":"https:\/\/doi.org\/10.3390\/cells10040789","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,2]]}}}