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Diabetes causes kidney cell‐specific mitochondrial phenotypes and increased generation of superoxide
Author(s) -
Rosca Mariana G,
Vazquez Edwin J,
Chen Qun,
Lee Chieh Allen,
Kern Timothy S,
Hoppel Charles L
Publication year - 2007
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.21.6.a841-b
Subject(s) - mitochondrion , superoxide , oxidative phosphorylation , biochemistry , chemistry , endocrinology , biology , glutamate dehydrogenase , medicine , malate dehydrogenase , glutamate receptor , enzyme , receptor
Mitochondrial induced oxidative stress causes cellular damage that leads to diabetic chronic complications. We hypothesized that cell‐ specific mitochondrial phenotypes develop in the diabetic kidney that predispose to increased production of superoxide by the mitochondrial electron transport chain. Glomerular and tubular mitochondria were isolated from control and streptozotocin‐induced diabetic rats. Diabetic glomerular mitochondria have higher abilities to oxidize glutamate and glutamate+malate, suggesting an increase in glutamate transporter or dehydrogenase, and malate/aspartate shuttling system respectively. Diabetic tubular mitochondria oxidize pyruvate at a lower rate, suggesting a decrease in the activity of either pyruvate dehydrogenase or transporter. In contrast, diabetic mitochondria have an increase in oxidative phosphorylation of both long‐ and medium chain fatty acid substrates that suggests an increase in fatty acid beta‐oxidation. This was associated with a larger amount of superoxide generated from the Qo site of the quinone cycle by tubular mitochondria oxidizing fat substrates. In conclusion, patterns of alteration in mitochondrial function occur in the diabetic kidney. They are cell‐specific, suggest a switch from glucose to fatty acid as source of mitochondrial ATP and cause increased superoxide production.