{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:52:17Z","timestamp":1784091137808,"version":"3.55.0"},"reference-count":124,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01 DK123264"],"award-info":[{"award-number":["R01 DK123264"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ischemia\u2010reperfusion injury (IRI) is a prevalent condition that predominantly afflicts hospitalized patients, inducing acute kidney injury (AKI). In recent years, complement 5 (C5) and its anaphylatoxin receptor C5aR1 have been implicated in driving kidney IRI and loss of function. Beyond this, prior studies suggest C5\u2010C5aR1 mediates mitochondrial ROS production, although its role in the mitochondria has never been fully characterized. Here, we leverage a previously generated model of C5 gene deletion (male C5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    rats) and the clinically relevant C5aR1 inhibitor Avacopan (AV) to investigate C5\u2010C5aR1 signaling in renal mitochondrial physiology and pathophysiology. For the first time, we report that C5\u2010C5aR1 axis inhibition modifies physiological mitochondrial protein levels, respiratory activity, and complexes\/supercomplexes. We identified a novel relationship between the C5\u2010C5aR1 axis and ATPase Inhibitory Factor 1 (IF1), a potent regulator of the ATP synthase, using in\u00a0vivo and in\u00a0vitro approaches. Post\u2010IRI, C5\u2010C5aR1 axis inhibition improved kidney function\/morphology and preserved ATP levels, despite IRI\u2010mediated disintegration of mitochondrial complexes and supercomplexes. We show in\u00a0vitro that C5\u2010C5aR1 axis inhibition facilitated IF1\u2010dependent ATP recovery via the glycolysis pathway. Collectively, our results demonstrate a complex interplay between C5\u2010C5aR1 and IF1 in renal mitochondria, which contributes to mitochondrial pathophysiology during IRI.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70942","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:00:56Z","timestamp":1780038056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel interactions between the\n                    <scp>C5<\/scp>\n                    \u2010\n                    <scp>C5aR<\/scp>\n                    1 Axis and\n                    <scp>IF<\/scp>\n                    1: Implications for kidney mitochondrial physiology and ischemia\u2013reperfusion injury"],"prefix":"10.14814","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5602-1982","authenticated-orcid":false,"given":"Madison","family":"McGraw","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amod","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Bhattarai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neriman","family":"Gokden","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LeeAnn","family":"Macmillan\u2010Crow","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3994-5338","authenticated-orcid":false,"given":"Nirmala","family":"Parajuli","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Toxicology University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"e_1_2_12_2_1","volume-title":"Annual Data Report","year":"2026"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201094946\u20103"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022111699"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000004996"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.05.012"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1210"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10050974"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523\u20101755.2003.00737.x"},{"key":"e_1_2_12_10_1","unstructured":"ATP Determination Kit 1 Kit | Buy Online | Invitrogen\u2122. (2026).ATP Determination Kit 1 Kit.https:\/\/www.thermofisher.com\/order\/catalog\/product\/A22066"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005\u2010019\u201000541\u2010w"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010020\u201000630\u20103"},{"key":"e_1_2_12_13_1","first-page":"293","article-title":"Kidney injury Molecule\u20101: A translational journey","volume":"125","author":"Bonventre J. V.","year":"2014","journal-title":"Transactions of the American Clinical and Climatological Association"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1903535116"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00258"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115314"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2017.06.002"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14262"},{"key":"e_1_2_12_19_1","volume-title":"Chronic Kidney Disease in the United States, 2023","author":"CDC","year":"2025"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.42"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010024\u201001843\u20105"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02084"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2005.11.015"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12405"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2005.02.023"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16051014"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010020\u20100400\u20100"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2014.304"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110851"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3791\/54985"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00153"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.05\u20104747com"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11248\u2010006\u20109002\u2010x"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.01.008"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi060339j"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.08.052"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/CRD.0000000000000496"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25094655"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw4852"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213880"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1324996"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.08.003"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc4915"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800987"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.17130"},{"key":"e_1_2_12_46_1","volume-title":"Study Reveals High Death Rates Associated With Acute Kidney Injury in Hospitalized Veterans","author":"Institute for Healthcare Policy and Innovation","year":"2026"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000004207"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.628062"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2023.130374"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2016.6635"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109\u2010020\u201002004\u20108"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470942390.mo150182"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2019.103580"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20231331"},{"key":"e_1_2_12_55_1","volume-title":"Complement Pathways: Types, Functions, Regulation","author":"Khanal S.","year":"2022"},{"key":"e_1_2_12_56_1","volume-title":"National Institute of Diabetes and Digestive and Kidney Diseases","author":"Kidney Disease Statistics for the United States\u2014NIDDK","year":"2026"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.37349\/ei.2024.00161"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201014444\u20103"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010019\u20100536\u20108"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102008\u201004\u2010151068"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1230381"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0161\u20105890(01)00044\u2010x"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00228.2016"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010024\u201001979\u20104"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology13060431"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12448"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.018"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00670.2020"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2010.12.008"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.12861\/jrip.2015.06"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102818.1993.tb03313.x"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.70576"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfaf135"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472\u20106823\u20109\u20102"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad068"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9010253"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf2489"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1159\/000520698"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2020.04.004"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.04.024"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185542"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00643.2013"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011111072"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.01.039"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0602\u2010582"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63503-1"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R113.472936"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891\u20105849(02)01111\u20105"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15238"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375\u2010025\u201002613\u20107"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310470"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.02.016"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2018.03.002"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.4103\/jpn.JPN_182_20"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.146480"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1993.212"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.10.020"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2017.10.007"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00281.2013"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu17132115"},{"issue":"1","key":"e_1_2_12_101_1","article-title":"Cold storage exacerbates renal and mitochondrial dysfunction following transplantation","volume":"2","author":"Shrum S.","year":"2016","journal-title":"Journal of Kidney"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2020.108410"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI163105"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010018\u20100107\u20102"},{"key":"e_1_2_12_105_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040620719874728"},{"key":"e_1_2_12_106_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20133244"},{"key":"e_1_2_12_107_1","unstructured":"TACS 2 TdT\u2010DAB. (2026).In Situ Apoptosis Detection Kit 4810\u201030\u2010K: R&D Systems.https:\/\/www.rndsystems.com\/products\/tacs\u20102\u2010tdt\u2010dab\u2010in\u2010situ\u2010apoptosis\u2010detection\u2010kit_4810\u201030\u2010k"},{"key":"e_1_2_12_108_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.7.4336"},{"key":"e_1_2_12_109_1","unstructured":"Tavneospro. (2023).TAVNEOS\u00ae (avacopan).https:\/\/www.tavneospro.com"},{"key":"e_1_2_12_110_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015\u2010023\u201010533\u20101"},{"key":"e_1_2_12_111_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.3.1517"},{"key":"e_1_2_12_112_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24521"},{"key":"e_1_2_12_113_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.102"},{"key":"e_1_2_12_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2020.100089"},{"key":"e_1_2_12_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2019.03.001"},{"key":"e_1_2_12_116_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.870811"},{"key":"e_1_2_12_117_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184465"},{"key":"e_1_2_12_118_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116722"},{"key":"e_1_2_12_119_1","doi-asserted-by":"publisher","DOI":"10.1177\/03946320241288426"},{"key":"e_1_2_12_120_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12111"},{"key":"e_1_2_12_121_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20106143.2006.01427.x"},{"key":"e_1_2_12_122_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI155333"},{"key":"e_1_2_12_123_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8621"},{"key":"e_1_2_12_124_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523\u20101755.2001.0590041227.x"},{"key":"e_1_2_12_125_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.110080"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70942","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.14814\/phy2.70942","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.70942","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T06:52:05Z","timestamp":1783839125000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.70942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":124,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.14814\/phy2.70942"],"URL":"https:\/\/doi.org\/10.14814\/phy2.70942","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"assertion":[{"value":"2026-03-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70942"}}