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Mammalian target of rapamycin regulate kidney oxygen consumption by controlling mitochondrial function via regulation of uncoupling protein 2
Author(s) -
Sivertsson Ebba,
Friederich Malou,
Palm Fredrik
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.687.1
Subject(s) - pi3k/akt/mtor pathway , mitochondrion , kidney , diabetic nephropathy , hypoxia (environmental) , renal function , chemistry , apoptosis , endocrinology , biology , medicine , microbiology and biotechnology , oxygen , biochemistry , organic chemistry
Excessive kidney oxygen consumption (QO 2 ) without concomitantly increased delivery results in tissue hypoxia, which is a common pathway to the development of kidney disease, including diabetic nephropathy. Mammalian target of rapamycin (mTOR) regulates cell proliferation but also mitochondrial function. However, the role for kidney QO 2 is presently unknown. We therefore investigated in vivo QO 2 and also studied specific mechanisms using isolated mitochondria from control and diabetic rats. Control and streptozotocin‐diabetic rats were administered rapamycin (0.15 mg/day) for 14 days. Kidney function was measured under Inactin anesthesia. Inhibition of mTOR increased kidney QO 2 (+121% and +31%) and decreased tubular transport efficiency (−50% and −36%) in both controls and diabetics without affecting glomerular filtration rate. mTOR inhibition increased QO 2 of isolated mitochondria by inducing uncoupling via uncoupling protein‐2. In conclusion, mTOR inhibition increases kidney QO 2 by inducing mitochondrial uncoupling, which may aggravate tissue hypoxia. Thus, mTOR inhibition in patients with pre‐existing nephropathy may accelerate the progression of disease.