Inhibition of insulin/IGF-1 receptor signaling protects from mitochondria-mediated kidney failure

摘要: Mitochondrial dysfunction and alterations in energy metabolism have been implicated a variety of human diseases. fusion is essential for maintenance mitochondrial function requires the prohibitin ring complex subunit prohibitin-2 (PHB2) at inner membrane. Here, we provide link between PHB2 deficiency hyperactive insulin/IGF-1 signaling. Deletion podocytes mice, terminally differentiated cells kidney filtration barrier, caused progressive proteinuria, failure, death animals resulted hyperphosphorylation S6 ribosomal protein (S6RP), known mediator mTOR signaling pathway. Inhibition system through genetic deletion insulin receptor alone or combination with IGF-1 treatment rapamycin prevented S6RP without affecting structural defect, alleviated renal disease, delayed onset failure PHB2-deficient animals. Evidently, perturbation contributes to tissue damage which may allow therapeutic intervention against wide spectrum