Journal article
Deficiency in apoptosis-inducing factor recapitulates chronic kidney disease via aberrant mitochondrial homeostasis
MT Coughlan, GC Higgins, TV Nguyen, SA Penfold, V Thallas-Bonke, SM Tan, G Ramm, NJ Van Bergen, DC Henstridge, KC Sourris, BE Harcourt, IA Trounce, PM Robb, A Laskowski, SL McGee, AJ Genders, K Walder, BG Drew, P Gregorevic, H Qian Show all
Diabetes | Published : 2016
DOI: 10.2337/db15-0864
Abstract
Apoptosis-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 upregul..
View full abstractGrants
Awarded by Juvenile Diabetes Research Foundation United States of America
Funding Acknowledgements
This work was completed with support from the National Health and Medical Research Council of Australia (NHMRC) (grant APP1023664) and the Victorian Governments Operational Infrastructure Support Program. M.T.C. has been supported by the Australian Diabetes Society Skip Martin Early Career Fellowship and the Australian and New Zealand Society of Nephrology Career Development Fellowship. G.C.H. is supported by a postdoctoral fellowship from JDRF. D.C.H. and L.A.G. have been supported by postdoctoral fellowships from the NHMRC/National Heart Foundation of Australia. S.L.M. is supported by an NHMRC Career, Development Fellowship. M.T.R., M.E.C., D.R.T., and J.M.F. are NHMRC Research Fellows.