{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:20:08Z","timestamp":1789874408916,"version":"4.0.1"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T00:00:00Z","timestamp":1666396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T00:00:00Z","timestamp":1666396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Clinical Research Plan of SHDC","award":["SHDC2020CR2041B"],"award-info":[{"award-number":["SHDC2020CR2041B"]}]},{"name":"Youth Project of the National Natural Science Fund","award":["81700851"],"award-info":[{"award-number":["81700851"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Oxidative stress-caused damage to the retinal pigment epithelium (RPE) underlies the onset and progression of age-related macular degeneration (AMD). Impaired mitochondrial biogenesis sensitizes RPE cells to mitochondrial dysfunction, energy insufficiency and death. Src-homology 2 domain-containing phosphatase (SHP)-1 is important in regulating immune responses and cell survival. However, its roles in cell survival are not always consistent. Until now, the effects of SHP-1 on RPE dysfunction, especially mitochondrial homeostasis, remain to be elucidated. We sought to clarify the effects of SHP-1 in RPE cells in response to atRAL-induced oxidative stress and determine the regulatory mechanisms involved.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In the all trans retinal\u00a0(atRAL)-induced oxidative stress model,\u00a0we used the vector of lentivirus to knockdown the expression of SHP-1\u00a0in ARPE-19 cells. CCK-8 assay, Annexin V\/PI staining and JC-1 staining were utilized to determine the cell viability, cell apoptosis and\u00a0mitochondrial membrane potential. We also used immunoprecipitation to examine the ubiquitination modification of stimulator of interferon genes (STING) and its interaction with SHP-1. The expression levels of mitochondrial marker, proteins related to mitochondrial biogenesis, and signaling molecules involved were examined by western blotting analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that SHP-1 knockdown predisposed RPE cells to apoptosis, aggravated mitochondrial damage, and repressed mitochondrial biogenesis after treatment with atRAL. Immunofluoresent staining and immunoprecipitation analysis confirmed that SHP-1 interacted with the endoplasmic reticulum-resident STING and suppressed K63-linked ubiquitination and activation of STING. Inhibition of STING with the specific antagonist H151 attenuated the effects of SHP-1 knockdown on mitochondrial biogenesis and oxidative damage. The adenosine monophosphate-activated protein kinase (AMPK) pathway acted as the crucial downstream target of STING and was involved in the regulatory processes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These findings suggest that SHP-1 knockdown potentiates STING overactivation and represses mitochondrial biogenesis and cell survival, at least in part by blocking the AMPK pathway in RPE cells. Therefore, restoring mitochondrial health by regulating SHP-1 in RPE cells may be a potential therapeutic strategy for degenerative retinal\u00a0diseases including AMD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10020-022-00554-w","type":"journal-article","created":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T21:02:53Z","timestamp":1666472573000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["SHP-1 knockdown suppresses mitochondrial biogenesis and aggravates mitochondria-dependent apoptosis induced by all trans retinal through the STING\/AMPK pathways"],"prefix":"10.1186","volume":"28","author":[{"given":"Xiaonan","family":"Zhuang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gezhi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5445-8004","authenticated-orcid":false,"given":"Zhongcui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,22]]},"reference":[{"issue":"1\u20132","key":"554_CR1","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.gene.2006.12.024","volume":"391","author":"JR Blesa","year":"2007","unstructured":"Blesa JR, Prieto-Ruiz JA, Hernandez JM, Hernandez-Yago J. NRF-2 transcription factor is required for human TOMM20 gene expression. Gene. 2007;391(1\u20132):198\u2013208. https:\/\/doi.org\/10.1016\/j.gene.2006.12.024.","journal-title":"Gene"},{"key":"554_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101201","volume":"24","author":"EE Brown","year":"2019","unstructured":"Brown EE, DeWeerd AJ, Ildefonso CJ, Lewin AS, Ash JD. Mitochondrial oxidative stress in the retinal pigment epithelium (RPE) led to metabolic dysfunction in both the RPE and retinal photoreceptors. Redox Biol. 2019;24: 101201. https:\/\/doi.org\/10.1016\/j.redox.2019.101201.","journal-title":"Redox Biol"},{"issue":"1","key":"554_CR3","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/cr.2009.141","volume":"20","author":"Y Cao","year":"2010","unstructured":"Cao Y, Li H, Liu H, Zheng C, Ji H, Liu X. The serine\/threonine kinase LKB1 controls thymocyte survival through regulation of AMPK activation and Bcl-XL expression. Cell Res. 2010;20(1):99\u2013108. https:\/\/doi.org\/10.1038\/cr.2009.141.","journal-title":"Cell Res"},{"issue":"2","key":"554_CR4","doi-asserted-by":"publisher","first-page":"E87","DOI":"10.1152\/ajpendo.00457.2019","volume":"318","author":"A Chaudhry","year":"2020","unstructured":"Chaudhry A, Shi R, Luciani DS. A pipeline for multidimensional confocal analysis of mitochondrial morphology, function, and dynamics in pancreatic beta-cells. Am J Physiol Endocrinol Metab. 2020;318(2):E87-101. https:\/\/doi.org\/10.1152\/ajpendo.00457.2019.","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"11","key":"554_CR5","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.14670\/HH-22.1251","volume":"22","author":"ZZ Chong","year":"2007","unstructured":"Chong ZZ, Maiese K. The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury. Histol Histopathol. 2007;22(11):1251\u201367. https:\/\/doi.org\/10.14670\/HH-22.1251.","journal-title":"Histol Histopathol"},{"issue":"1","key":"554_CR6","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s13238-015-0222-9","volume":"7","author":"C Fang","year":"2016","unstructured":"Fang C, Wei X, Wei Y. Mitochondrial DNA in the regulation of innate immune responses. Protein Cell. 2016;7(1):11\u20136. https:\/\/doi.org\/10.1007\/s13238-015-0222-9.","journal-title":"Protein Cell"},{"issue":"7","key":"554_CR7","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.neurobiolaging.2005.05.012","volume":"27","author":"J Feher","year":"2006","unstructured":"Feher J, Kovacs I, Artico M, Cavallotti C, Papale A, Balacco GC. Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration. Neurobiol Aging. 2006;27(7):983\u201393. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2005.05.012.","journal-title":"Neurobiol Aging"},{"key":"554_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.redox.2018.09.011","volume":"20","author":"S Felszeghy","year":"2019","unstructured":"Felszeghy S, Viiri J, Paterno JJ, Hyttinen J, Koskela A, Chen M, et al. Loss of NRF-2 and PGC-1alpha genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration. Redox Biol. 2019;20:1\u201312. https:\/\/doi.org\/10.1016\/j.redox.2018.09.011.","journal-title":"Redox Biol"},{"issue":"4","key":"554_CR9","doi-asserted-by":"publisher","first-page":"F608","DOI":"10.1152\/ajprenal.00554.2020","volume":"320","author":"W Gong","year":"2021","unstructured":"Gong W, Lu L, Zhou Y, Liu J, Ma H, Fu L, et al. The novel STING antagonist H151 ameliorates cisplatin-induced acute kidney injury and mitochondrial dysfunction. Am J Physiol Renal Physiol. 2021;320(4):F608\u201316. https:\/\/doi.org\/10.1152\/ajprenal.00554.2020.","journal-title":"Am J Physiol Renal Physiol"},{"issue":"10","key":"554_CR10","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1002\/glia.22842","volume":"63","author":"RC Gruber","year":"2015","unstructured":"Gruber RC, LaRocca D, Minchenberg SB, Christophi GP, Hudson CA, Ray AK, et al. The control of reactive oxygen species production by SHP-1 in oligodendrocytes. Glia. 2015;63(10):1753\u201371. https:\/\/doi.org\/10.1002\/glia.22842.","journal-title":"Glia"},{"issue":"7713","key":"554_CR11","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41586-018-0287-8","volume":"559","author":"SM Haag","year":"2018","unstructured":"Haag SM, Gulen MF, Reymond L, Gibelin A, Abrami L, Decout A, et al. Targeting STING with covalent small-molecule inhibitors. Nature. 2018;559(7713):269\u201373. https:\/\/doi.org\/10.1038\/s41586-018-0287-8.","journal-title":"Nature"},{"issue":"9","key":"554_CR12","doi-asserted-by":"publisher","first-page":"12392","DOI":"10.1096\/fj.202000600RR","volume":"34","author":"D Hao","year":"2020","unstructured":"Hao D, Wang Y, Li L, Qian G, Liu J, Li M, et al. SHP-1 suppresses the antiviral innate immune response by targeting TRAF3. Faseb J. 2020;34(9):12392\u2013405. https:\/\/doi.org\/10.1096\/fj.202000600RR.","journal-title":"Faseb J"},{"key":"554_CR13","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/978-1-4419-1399-9_20","volume":"664","author":"Y He","year":"2010","unstructured":"He Y, Tombran-Tink J. Mitochondrial decay and impairment of antioxidant defenses in aging RPE cells. Adv Exp Med Biol. 2010;664:165\u201383. https:\/\/doi.org\/10.1007\/978-1-4419-1399-9_20.","journal-title":"Adv Exp Med Biol"},{"issue":"2","key":"554_CR14","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrm.2017.95","volume":"19","author":"S Herzig","year":"2018","unstructured":"Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018;19(2):121\u201335. https:\/\/doi.org\/10.1038\/nrm.2017.95.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"554_CR15","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.exer.2018.02.023","volume":"170","author":"J Hua","year":"2018","unstructured":"Hua J, Chen H, Chen Y, Zheng G, Li F, Qu J, et al. MITF acts as an anti-oxidant transcription factor to regulate mitochondrial biogenesis and redox signaling in retinal pigment epithelial cells. Exp Eye Res. 2018;170:138\u201347. https:\/\/doi.org\/10.1016\/j.exer.2018.02.023.","journal-title":"Exp Eye Res"},{"issue":"7265","key":"554_CR16","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/nature08476","volume":"461","author":"H Ishikawa","year":"2009","unstructured":"Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature. 2009;461(7265):788\u201392. https:\/\/doi.org\/10.1038\/nature08476.","journal-title":"Nature"},{"issue":"9","key":"554_CR17","doi-asserted-by":"publisher","first-page":"5402","DOI":"10.1074\/jbc.M706462200","volume":"283","author":"SH Jia","year":"2008","unstructured":"Jia SH, Parodo J, Kapus A, Rotstein OD, Marshall JC. Dynamic regulation of neutrophil survival through tyrosine phosphorylation or dephosphorylation of caspase-8. J Biol Chem. 2008;283(9):5402\u201313. https:\/\/doi.org\/10.1074\/jbc.M706462200.","journal-title":"J Biol Chem"},{"key":"554_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100858","volume":"79","author":"K Kaarniranta","year":"2020","unstructured":"Kaarniranta K, Uusitalo H, Blasiak J, Felszeghy S, Kannan R, Kauppinen A, et al. Mechanisms of mitochondrial dysfunction and their impact on age-related macular degeneration. Prog Retin Eye Res. 2020;79: 100858. https:\/\/doi.org\/10.1016\/j.preteyeres.2020.100858.","journal-title":"Prog Retin Eye Res"},{"issue":"1","key":"554_CR19","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nm.4450","volume":"24","author":"N Kerur","year":"2018","unstructured":"Kerur N, Fukuda S, Banerjee D, Kim Y, Fu D, Apicella I, et al. cGAS drives noncanonical-inflammasome activation in age-related macular degeneration. Nat Med. 2018;24(1):50\u201361. https:\/\/doi.org\/10.1038\/nm.4450.","journal-title":"Nat Med"},{"issue":"2","key":"554_CR20","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.jconrel.2013.02.031","volume":"168","author":"D Kim","year":"2013","unstructured":"Kim D, Hong J, Moon HH, Nam HY, Mok H, Jeong JH, et al. Anti-apoptotic cardioprotective effects of SHP-1 gene silencing against ischemia-reperfusion injury: use of deoxycholic acid-modified low molecular weight polyethyleneimine as a cardiac siRNA-carrier. J Control Release. 2013;168(2):125\u201334. https:\/\/doi.org\/10.1016\/j.jconrel.2013.02.031.","journal-title":"J Control Release"},{"issue":"1","key":"554_CR21","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.bbalip.2011.03.005","volume":"1821","author":"PD Kiser","year":"2012","unstructured":"Kiser PD, Golczak M, Maeda A, Palczewski K. Key enzymes of the retinoid (visual) cycle in vertebrate retina. Biochim Biophys Acta. 2012;1821(1):137\u201351. https:\/\/doi.org\/10.1016\/j.bbalip.2011.03.005.","journal-title":"Biochim Biophys Acta"},{"issue":"10","key":"554_CR22","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1016\/j.jacc.2005.02.039","volume":"45","author":"F Krotz","year":"2005","unstructured":"Krotz F, Engelbrecht B, Buerkle MA, Bassermann F, Bridell H, Gloe T, et al. The tyrosine phosphatase, SHP-1, is a negative regulator of endothelial superoxide formation. J Am Coll Cardiol. 2005;45(10):1700\u20136. https:\/\/doi.org\/10.1016\/j.jacc.2005.02.039.","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"554_CR23","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1093\/toxsci\/kfu223","volume":"143","author":"J Li","year":"2015","unstructured":"Li J, Cai X, Xia Q, Yao K, Chen J, Zhang Y, et al. Involvement of endoplasmic reticulum stress in all-trans-retinal-induced retinal pigment epithelium degeneration. Toxicol Sci. 2015;143(1):196\u2013208. https:\/\/doi.org\/10.1093\/toxsci\/kfu223.","journal-title":"Toxicol Sci"},{"issue":"6227","key":"554_CR24","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa2630","volume":"347","author":"S Liu","year":"2015","unstructured":"Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science. 2015;347(6227): a2630. https:\/\/doi.org\/10.1126\/science.aaa2630.","journal-title":"Science"},{"issue":"2","key":"554_CR25","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/ni.3641","volume":"18","author":"B Liu","year":"2017","unstructured":"Liu B, Zhang M, Chu H, Zhang H, Wu H, Song G, et al. The ubiquitin E3 ligase TRIM31 promotes aggregation and activation of the signaling adaptor MAVS through Lys63-linked polyubiquitination. Nat Immunol. 2017;18(2):214\u201324. https:\/\/doi.org\/10.1038\/ni.3641.","journal-title":"Nat Immunol"},{"issue":"3","key":"554_CR26","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1167\/iovs.05-1161","volume":"47","author":"BL Lyons","year":"2006","unstructured":"Lyons BL, Smith RS, Hurd RE, Hawes NL, Burzenski LM, Nusinowitz S, et al. Deficiency of SHP-1 protein-tyrosine phosphatase in \u201cviable motheaten\u201d mice results in retinal degeneration. Invest Ophthalmol vis Sci. 2006;47(3):1201\u20139. https:\/\/doi.org\/10.1167\/iovs.05-1161.","journal-title":"Invest Ophthalmol vis Sci"},{"issue":"39","key":"554_CR27","doi-asserted-by":"publisher","first-page":"26684","DOI":"10.1074\/jbc.M804505200","volume":"283","author":"A Maeda","year":"2008","unstructured":"Maeda A, Maeda T, Golczak M, Palczewski K. Retinopathy in mice induced by disrupted all-trans-retinal clearance. J Biol Chem. 2008;283(39):26684\u201393. https:\/\/doi.org\/10.1074\/jbc.M804505200.","journal-title":"J Biol Chem"},{"issue":"22","key":"554_CR28","doi-asserted-by":"publisher","first-page":"15173","DOI":"10.1074\/jbc.M900322200","volume":"284","author":"A Maeda","year":"2009","unstructured":"Maeda A, Maeda T, Golczak M, Chou S, Desai A, Hoppel CL, et al. Involvement of all-trans-retinal in acute light-induced retinopathy of mice. J Biol Chem. 2009;284(22):15173\u201383. https:\/\/doi.org\/10.1074\/jbc.M900322200.","journal-title":"J Biol Chem"},{"issue":"7","key":"554_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.348","volume":"8","author":"S Nashine","year":"2017","unstructured":"Nashine S, Cohen P, Chwa M, Lu S, Nesburn AB, Kuppermann BD, et al. Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage. Cell Death Dis. 2017;8(7): e2951. https:\/\/doi.org\/10.1038\/cddis.2017.348.","journal-title":"Cell Death Dis"},{"issue":"1","key":"554_CR30","doi-asserted-by":"publisher","first-page":"e103","DOI":"10.1111\/aos.13812","volume":"97","author":"C Nunez-Alvarez","year":"2019","unstructured":"Nunez-Alvarez C, Suarez-Barrio C, Del OAS, Osborne NN. Blue light negatively affects the survival of ARPE19 cells through an action on their mitochondria and blunted by red light. Acta Ophthalmol. 2019;97(1):e103\u201315. https:\/\/doi.org\/10.1111\/aos.13812.","journal-title":"Acta Ophthalmol"},{"issue":"6","key":"554_CR31","doi-asserted-by":"publisher","first-page":"e228","DOI":"10.1111\/j.1755-3768.2010.01945.x","volume":"88","author":"T Papadaki","year":"2010","unstructured":"Papadaki T, Tsilimbaris M, Pallikaris I, Thermos K. Somatostatin receptor activation (sst(1) -sst(5) ) differentially influences human retinal pigment epithelium cell viability. Acta Ophthalmol. 2010;88(6):e228\u201333. https:\/\/doi.org\/10.1111\/j.1755-3768.2010.01945.x.","journal-title":"Acta Ophthalmol"},{"issue":"12","key":"554_CR32","doi-asserted-by":"publisher","first-page":"712","DOI":"10.5483\/BMBRep.2019.52.12.249","volume":"52","author":"SH Park","year":"2019","unstructured":"Park SH, Lee AR, Choi K, Joung S, Yoon JB, Kim S. TOMM20 as a potential therapeutic target of colorectal cancer. Bmb Rep. 2019;52(12):712\u20137.","journal-title":"Bmb Rep"},{"issue":"1","key":"554_CR33","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12974-020-01830-4","volume":"17","author":"Y Peng","year":"2020","unstructured":"Peng Y, Zhuang J, Ying G, Zeng H, Zhou H, Cao Y, et al. Stimulator of IFN genes mediates neuroinflammatory injury by suppressing AMPK signal in experimental subarachnoid hemorrhage. J Neuroinflammation. 2020;17(1):165. https:\/\/doi.org\/10.1186\/s12974-020-01830-4.","journal-title":"J Neuroinflammation"},{"issue":"41","key":"554_CR34","doi-asserted-by":"publisher","first-page":"16544","DOI":"10.1073\/pnas.1308331110","volume":"110","author":"J Petrasek","year":"2013","unstructured":"Petrasek J, Iracheta-Vellve A, Csak T, Satishchandran A, Kodys K, Kurt-Jones EA, et al. STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease. Proc Natl Acad Sci U S A. 2013;110(41):16544\u20139. https:\/\/doi.org\/10.1073\/pnas.1308331110.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"554_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.celrep.2017.09.026","volume":"21","author":"RC Rabinovitch","year":"2017","unstructured":"Rabinovitch RC, Samborska B, Faubert B, Ma EH, Gravel SP, Andrzejewski S, et al. AMPK maintains cellular metabolic homeostasis through regulation of mitochondrial reactive oxygen species. Cell Rep. 2017;21(1):1\u20139. https:\/\/doi.org\/10.1016\/j.celrep.2017.09.026.","journal-title":"Cell Rep"},{"issue":"9","key":"554_CR36","doi-asserted-by":"publisher","first-page":"5354","DOI":"10.1167\/iovs.12-9845","volume":"53","author":"F Schutt","year":"2012","unstructured":"Schutt F, Aretz S, Auffarth GU, Kopitz J. Moderately reduced ATP levels promote oxidative stress and debilitate autophagic and phagocytic capacities in human RPE cells. Invest Ophthalmol vis Sci. 2012;53(9):5354\u201361. https:\/\/doi.org\/10.1167\/iovs.12-9845.","journal-title":"Invest Ophthalmol vis Sci"},{"issue":"3","key":"554_CR37","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1167\/iovs.15-17053","volume":"57","author":"PG Sreekumar","year":"2016","unstructured":"Sreekumar PG, Ishikawa K, Spee C, Mehta HH, Wan J, Yen K, et al. The mitochondrial-derived peptide humanin protects RPE cells from oxidative stress, senescence, and mitochondrial dysfunction. Invest Ophthalmol vis Sci. 2016;57(3):1238\u201353. https:\/\/doi.org\/10.1167\/iovs.15-17053.","journal-title":"Invest Ophthalmol vis Sci"},{"issue":"Pt 3","key":"554_CR38","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1042\/bj3450437","volume":"345","author":"SC Stein","year":"2000","unstructured":"Stein SC, Woods A, Jones NA, Davison MD, Carling D. The regulation of AMP-activated protein kinase by phosphorylation. Biochem J. 2000;345(Pt 3):437\u201343.","journal-title":"Biochem J"},{"issue":"214","key":"554_CR39","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2002521","volume":"5","author":"Y Tanaka","year":"2012","unstructured":"Tanaka Y, Chen ZJ. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci Signal. 2012;5(214): a20. https:\/\/doi.org\/10.1126\/scisignal.2002521.","journal-title":"Sci Signal."},{"issue":"4","key":"554_CR40","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1078\/S0171-9335(04)70029-1","volume":"79","author":"T Tenev","year":"2000","unstructured":"Tenev T, Bohmer SA, Kaufmann R, Frese S, Bittorf T, Beckers T, et al. Perinuclear localization of the protein-tyrosine phosphatase SHP-1 and inhibition of epidermal growth factor-stimulated STAT1\/3 activation in A431 cells. Eur J Cell Biol. 2000;79(4):261\u201371. https:\/\/doi.org\/10.1078\/S0171-9335(04)70029-1.","journal-title":"Eur J Cell Biol"},{"issue":"18","key":"554_CR41","doi-asserted-by":"publisher","first-page":"7304","DOI":"10.1523\/JNEUROSCI.0190-15.2015","volume":"35","author":"MR Terluk","year":"2015","unstructured":"Terluk MR, Kapphahn RJ, Soukup LM, Gong H, Gallardo C, Montezuma SR, et al. Investigating mitochondria as a target for treating age-related macular degeneration. J Neurosci. 2015;35(18):7304\u201311. https:\/\/doi.org\/10.1523\/JNEUROSCI.0190-15.2015.","journal-title":"J Neurosci"},{"issue":"2","key":"554_CR42","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.bbrc.2019.03.187","volume":"513","author":"H Tian","year":"2019","unstructured":"Tian H, Tan R, Ye B, Yan S, Sui M, Zhao W, et al. SHP-1 inhibits renal ischemia reperfusion injury via dephosphorylating ASK1 and suppressing apoptosis. Biochem Biophys Res Commun. 2019;513(2):360\u20137. https:\/\/doi.org\/10.1016\/j.bbrc.2019.03.187.","journal-title":"Biochem Biophys Res Commun"},{"key":"554_CR43","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.preteyeres.2018.03.005","volume":"66","author":"SK Verbakel","year":"2018","unstructured":"Verbakel SK, van Huet R, Boon C, den Hollander AI, Collin R, Klaver C, et al. Non-syndromic retinitis pigmentosa. Prog Retin Eye Res. 2018;66:157\u201386. https:\/\/doi.org\/10.1016\/j.preteyeres.2018.03.005.","journal-title":"Prog Retin Eye Res"},{"issue":"22","key":"554_CR44","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019104106","volume":"39","author":"C Wang","year":"2020","unstructured":"Wang C, Wang X, Veleeparambil M, Kessler PM, Willard B, Chattopadhyay S, et al. EGFR-mediated tyrosine phosphorylation of STING determines its trafficking route and cellular innate immunity functions. Embo J. 2020;39(22): e104106. https:\/\/doi.org\/10.15252\/embj.2019104106.","journal-title":"Embo J"},{"issue":"1","key":"554_CR45","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/s41423-021-00802-9","volume":"19","author":"Y Wang","year":"2022","unstructured":"Wang Y, Qian G, Zhu L, Zhao Z, Liu Y, Han W, et al. HIV-1 Vif suppresses antiviral immunity by targeting STING. Cell Mol Immunol. 2022;19(1):108\u201321. https:\/\/doi.org\/10.1038\/s41423-021-00802-9.","journal-title":"Cell Mol Immunol"},{"issue":"2","key":"554_CR46","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","volume":"2","author":"WL Wong","year":"2014","unstructured":"Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106\u201316. https:\/\/doi.org\/10.1016\/S2214-109X(13)70145-1.","journal-title":"Lancet Glob Health"},{"issue":"1","key":"554_CR47","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0092-8674(00)80611-X","volume":"98","author":"Z Wu","year":"1999","unstructured":"Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98(1):115\u201324. https:\/\/doi.org\/10.1016\/S0092-8674(00)80611-X.","journal-title":"Cell"},{"issue":"4","key":"554_CR48","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/j.bbagen.2013.10.034","volume":"1840","author":"SB Wu","year":"2014","unstructured":"Wu SB, Wu YT, Wu TP, Wei YH. Role of AMPK-mediated adaptive responses in human cells with mitochondrial dysfunction to oxidative stress. Biochim Biophys Acta. 2014;1840(4):1331\u201344. https:\/\/doi.org\/10.1016\/j.bbagen.2013.10.034.","journal-title":"Biochim Biophys Acta"},{"key":"554_CR49","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1172\/jci.insight.145029","volume":"6","author":"DM Wu","year":"2021","unstructured":"Wu DM, Ji X, Ivanchenko MV, Chung M, Piper M, Rana P, et al. Nrf2 overexpression rescues the RPE in mouse models of retinitis pigmentosa. JCI Insight. 2021;6:2. https:\/\/doi.org\/10.1172\/jci.insight.145029.","journal-title":"JCI Insight."},{"issue":"4","key":"554_CR50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007680","volume":"15","author":"L Ye","year":"2019","unstructured":"Ye L, Zhang Q, Liuyu T, Xu Z, Zhang MX, Luo MH, et al. USP49 negatively regulates cellular antiviral responses via deconjugating K63-linked ubiquitination of MITA. Plos Pathog. 2019;15(4): e1007680. https:\/\/doi.org\/10.1371\/journal.ppat.1007680.","journal-title":"Plos Pathog"},{"issue":"3","key":"554_CR51","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/s1044-5323(03)00033-2","volume":"15","author":"S Yousefi","year":"2003","unstructured":"Yousefi S, Simon HU. SHP-1: a regulator of neutrophil apoptosis. Semin Immunol. 2003;15(3):195\u20139. https:\/\/doi.org\/10.1016\/s1044-5323(03)00033-2.","journal-title":"Semin Immunol"},{"issue":"8","key":"554_CR52","doi-asserted-by":"publisher","first-page":"3846","DOI":"10.1167\/iovs.06-1145","volume":"48","author":"N Zhang","year":"2007","unstructured":"Zhang N, Peairs JJ, Yang P, Tyrrell J, Roberts J, Kole R, et al. The importance of Bcl-xL in the survival of human RPE cells. Invest Ophthalmol vis Sci. 2007;48(8):3846\u201353. https:\/\/doi.org\/10.1167\/iovs.06-1145.","journal-title":"Invest Ophthalmol vis Sci"},{"issue":"43","key":"554_CR53","doi-asserted-by":"publisher","first-page":"13839","DOI":"10.1021\/jp103547s","volume":"114","author":"Y Zhang","year":"2010","unstructured":"Zhang Y, Baaden M, Yan J, Shao J, Qiu S, Wu Y, et al. The molecular recognition mechanism for superoxide dismutase presequence binding to the mitochondrial protein import receptor Tom20 from Oryza sativa involves an LRTLA motif. J Phys Chem B. 2010;114(43):13839\u201346. https:\/\/doi.org\/10.1021\/jp103547s.","journal-title":"J Phys Chem B"},{"issue":"1","key":"554_CR54","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1038\/s41392-021-00613-4","volume":"6","author":"R Zhang","year":"2021","unstructured":"Zhang R, Kang R, Tang D. The STING1 network regulates autophagy and cell death. Signal Transduct Target Ther. 2021;6(1):208. https:\/\/doi.org\/10.1038\/s41392-021-00613-4.","journal-title":"Signal Transduct Target Ther"},{"issue":"4","key":"554_CR55","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.cell.2018.01.007","volume":"172","author":"P Zhao","year":"2018","unstructured":"Zhao P, Wong KI, Sun X, Reilly SM, Uhm M, Liao Z, et al. TBK1 at the Crossroads of Inflammation and Energy Homeostasis in Adipose Tissue. Cell. 2018;172(4):731\u201343. https:\/\/doi.org\/10.1016\/j.cell.2018.01.007.","journal-title":"Cell"},{"issue":"3","key":"554_CR56","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.immuni.2009.01.008","volume":"30","author":"B Zhong","year":"2009","unstructured":"Zhong B, Zhang L, Lei C, Li Y, Mao AP, Yang Y, et al. The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. Immunity. 2009;30(3):397\u2013407. https:\/\/doi.org\/10.1016\/j.immuni.2009.01.008.","journal-title":"Immunity"},{"issue":"1","key":"554_CR57","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1080\/22221751.2019.1620589","volume":"8","author":"R Zhou","year":"2019","unstructured":"Zhou R, Chen Z, Hao D, Wang Y, Zhang Y, Yi X, et al. Enterohemorrhagic Escherichia coli Tir inhibits TAK1 activation and mediates immune evasion. Emerg Microbes Infect. 2019;8(1):734\u201348. https:\/\/doi.org\/10.1080\/22221751.2019.1620589.","journal-title":"Emerg Microbes Infect."}],"container-title":["Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-022-00554-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10020-022-00554-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-022-00554-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T21:04:52Z","timestamp":1666472692000},"score":1,"resource":{"primary":{"URL":"https:\/\/molmed.biomedcentral.com\/articles\/10.1186\/s10020-022-00554-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,22]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["554"],"URL":"https:\/\/doi.org\/10.1186\/s10020-022-00554-w","relation":{},"ISSN":["1076-1551","1528-3658"],"issn-type":[{"value":"1076-1551","type":"print"},{"value":"1528-3658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,22]]},"assertion":[{"value":"6 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The animal experiments were in accordance with ARVO Statement on the Use of Animals in Research and were approved by the Animal Ethics Committee of the Eye and Ear Nose Throat Hospital of Fudan University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"125"}}