Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/19243
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dc.contributor.authorCoughlan, Melinda T-
dc.contributor.authorHiggins, Gavin C-
dc.contributor.authorNguyen, Tuong-Vi-
dc.contributor.authorPenfold, Sally A-
dc.contributor.authorThallas-Bonke, Vicki-
dc.contributor.authorTan, Sih Min-
dc.contributor.authorRamm, Georg-
dc.contributor.authorVan Bergen, Nicole J-
dc.contributor.authorHenstridge, Darren C-
dc.contributor.authorSourris, Karly C-
dc.contributor.authorHarcourt, Brooke E-
dc.contributor.authorTrounce, Ian A-
dc.contributor.authorRobb, Portia M-
dc.contributor.authorLaskowski, Adrienne-
dc.contributor.authorMcGee, Sean L-
dc.contributor.authorGenders, Amanda J-
dc.contributor.authorWalder, Ken-
dc.contributor.authorDrew, Brian G-
dc.contributor.authorGregorevic, Paul-
dc.contributor.authorQian, Hongwei-
dc.contributor.authorThomas, Merlin C-
dc.contributor.authorJerums, George-
dc.contributor.authorMacIsaac, Richard J-
dc.contributor.authorSkene, Alison-
dc.contributor.authorPower, David A-
dc.contributor.authorEkinci, Elif I-
dc.contributor.authorWijeyeratne, Xiaonan W-
dc.contributor.authorGallo, Linda A-
dc.contributor.authorHerman-Edelstein, Michal-
dc.contributor.authorRyan, Michael T-
dc.contributor.authorCooper, Mark E-
dc.contributor.authorThorburn, David R-
dc.contributor.authorForbes, Josephine M-
dc.date2016-01-28-
dc.date.accessioned2018-09-13T00:21:15Z-
dc.date.available2018-09-13T00:21:15Z-
dc.date.issued2016-04-
dc.identifier.citationDiabetes 2016; 65(4): 1085-1098-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/19243-
dc.description.abstractApoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with dual roles in redox signaling and programmed cell death. Deficiency in AIF is known to result in defective oxidative phosphorylation (OXPHOS), via loss of complex I activity and assembly in other tissues. Because the kidney relies on OXPHOS for metabolic homeostasis, we hypothesized that a decrease in AIF would result in chronic kidney disease (CKD). Here, we report that partial knockdown of Aif in mice recapitulates many features of CKD, in association with a compensatory increase in the mitochondrial ATP pool via a shift toward mitochondrial fusion, excess mitochondrial reactive oxygen species production, and Nox4 upregulation. However, despite a 50% lower AIF protein content in the kidney cortex, there was no loss of complex I activity or assembly. When diabetes was superimposed onto Aif knockdown, there were extensive changes in mitochondrial function and networking, which augmented the renal lesion. Studies in patients with diabetic nephropathy showed a decrease in AIF within the renal tubular compartment and lower AIFM1 renal cortical gene expression, which correlated with declining glomerular filtration rate. Lentiviral overexpression of Aif1m rescued glucose-induced disruption of mitochondrial respiration in human primary proximal tubule cells. These studies demonstrate that AIF deficiency is a risk factor for the development of diabetic kidney disease.-
dc.language.isoeng-
dc.titleDeficiency in Apoptosis-Inducing Factor Recapitulates Chronic Kidney Disease via Aberrant Mitochondrial Homeostasis.-
dc.typeJournal Article-
dc.identifier.journaltitleDiabetes-
dc.identifier.affiliationMenzies School of Health Research, Darwin, Northern Territory, Australiaen
dc.identifier.affiliationBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia Glycation and Diabetes Group, Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, South Brisbane, Queensland, Australiaen
dc.identifier.affiliationSchool of Medicine, Mater Clinical School, The University of Queensland, St. Lucia, Queensland, Australiaen
dc.identifier.affiliationBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia Department of Medicine, Central Clinical School, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australiaen
dc.identifier.affiliationDepartment of Epidemiology and Preventive Medicine, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australiaen
dc.identifier.affiliationDepartment of Nephrology, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationInstitute for Breathing and Sleep, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationGlycation and Diabetes Group, Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, South Brisbane, Queensland, Australiaen
dc.identifier.affiliationThe Felsenstein Medical Research Center and Department of Nephrology and Hypertension, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israelen
dc.identifier.affiliationMitochondria Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australiaen
dc.identifier.affiliationBaker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australiaen
dc.identifier.affiliationMembrane Biology Group, Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medicine, Central Clinical School, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australiaen
dc.identifier.affiliationMurdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australiaen
dc.identifier.affiliationCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australiaen
dc.identifier.affiliationMetabolic Research Unit, Deakin University, Waurn Ponds, Victoria, Australiaen
dc.identifier.affiliationEndocrine Centre, Heidelberg Repatriation Hospital, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartments of Endocrinology and Diabetes, St Vincent's Hospital Melbourne and The University of Melbourne, Fitzroy, Victoria, Australiaen
dc.identifier.affiliationDepartment of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationDepartment of Biochemistry, La Trobe University, Melbourne, Victoria, Australiaen
dc.identifier.doi10.2337/db15-0864-
dc.identifier.orcid0000-0003-2372-395X-
dc.identifier.pubmedid26822084-
dc.type.austinJournal Article-
dc.type.austinResearch Support, Non-U.S. Gov't-
local.name.researcherEkinci, Elif I
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptEndocrinology-
crisitem.author.deptPathology-
crisitem.author.deptMedicine (University of Melbourne)-
crisitem.author.deptInstitute for Breathing and Sleep-
crisitem.author.deptEndocrinology-
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