In:
EMBO Molecular Medicine, EMBO, Vol. 7, No. 3 ( 2015-03), p. 275-287
Abstract:
image Podocyte‐specific PHB 2 loss results in severe kidney disease that is alleviated by insulin and IGF ‐1 receptors deletion or rapamycin treatment, demonstrating not only a causal link between mitochondrial dysfunction and kidney disease but also putative therapeutic avenues. Deletion of the mitochondrial protein PHB 2 in glomerular podocytes caused progressive proteinuria and death of the animals due to end‐stage kidney failure. Contrary to generally held beliefs loss of PHB 2 did not cause overt defects in mitochondrial respiratory activity or increased production of ROS but was accompanied by hyperactive insulin/ IGF ‐1 receptor signaling. Inhibition of the insulin/IGF‐1 signaling system through genetic deletion of insulin receptor alone or in combination with the IGF‐1 receptor or treatment with mTOR inhibitor rapamycin, alleviated renal disease and delayed the onset of kidney failure in PHB2‐deficient animals.
Type of Medium:
Online Resource
ISSN:
1757-4676
,
1757-4684
DOI:
10.15252/emmm.201404916
Language:
English
Publisher:
EMBO
Publication Date:
2015
detail.hit.zdb_id:
2485479-7
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