Friederich-Persson 2018 Acta Physiol (Oxf)
|Friederich-Persson M, Persson P, Hansell P, Palm F (2018) Deletion of Uncoupling Protein-2 reduces renal mitochondrial leak respiration, intrarenal hypoxia and proteinuria in a mouse model of type 1 diabetes. Acta Physiol (Oxf) 223:e13058.
Abstract: Uncoupling protein-2 (UCP-2) can induce mitochondrial uncoupling in the diabetic kidney. Although mitochondrial uncoupling reduces oxidative stress originating from the mitochondria and can be regarded as a protective mechanism, the increased oxygen consumption occurring secondarily to increased mitochondria uncoupling, that is leak respiration, may contribute to kidney tissue hypoxia. Using UCP-2-/- mice, we tested the hypothesis that UCP-2-mediated leak respiration is important for the development of diabetes-induced intrarenal hypoxia and proteinuria.
Kidney function, in vivo oxygen metabolism, urinary protein leakage and mitochondrial function were determined in wild-type and UCP-2-/- mice during normoglycaemia and 2 weeks after diabetes induction.
Diabetic wild-type mice displayed mitochondrial leak respiration, pronounced intrarenal hypoxia, proteinuria and increased urinary KIM-1 excretion. However, diabetic UCP-2-/- mice did not develop increased mitochondrial leak respiration and presented with normal intrarenal oxygen levels, urinary protein and KIM-1 excretion.
Although functioning as an antioxidant system, mitochondria uncoupling is always in co-occurrence with increased oxygen consumption, that is leak respiration; a potentially detrimental side effect as it can result in kidney tissue hypoxia; an acknowledged unifying pathway to nephropathy. Indeed, this study demonstrates a novel mechanism in which UCP-2-mediated mitochondrial leak respiration is necessary for the development of diabetes-induced intrarenal tissue hypoxia and proteinuria.
© 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd. • Keywords: Diabetic nephropathy, Kidney, Kidney injury molecule-1, Mitochondria, Oxygen consumption • Bioblast editor: Kandolf G • O2k-Network Lab: SE Uppsala Liss P
Labels: MiParea: Respiration Pathology: Diabetes Stress:Hypoxia Organism: Mouse Tissue;cell: Kidney Preparation: Isolated mitochondria Enzyme: Uncoupling protein
Coupling state: LEAK, OXPHOS Pathway: N HRR: Oxygraph-2k