Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2004 Apr;286(4):F749-59.
doi: 10.1152/ajprenal.00276.2003. Epub 2003 Dec 9.

Preservation of complex I function during hypoxia-reoxygenation-induced mitochondrial injury in proximal tubules

Thorsten Feldkamp  1 , Andreas Kribben, Nancy F Roeser, Ruth A Senter, Sarah Kemner, Manjeri A Venkatachalam, Itzhak Nissim, Joel M Weinberg
Affiliations
Free article

Preservation of complex I function during hypoxia-reoxygenation-induced mitochondrial injury in proximal tubules

Thorsten Feldkamp et al. Am J Physiol Renal Physiol. 2004 Apr.
Free article

Abstract

Inhibition of complex I has been considered to be an important contributor to mitochondrial dysfunction in tissues subjected to ischemia-reperfusion. We have investigated the role of complex I in a severe energetic deficit that develops in kidney proximal tubules subjected to hypoxia-reoxygenation and is strongly ameliorated by supplementation with specific citric acid cycle metabolites, including succinate and the combination of -ketoglutarate plus malate. NADH: ubiquinone reductase activity in the tubules was decreased by only 26% during 60-min hypoxia and did not change further during 60-min reoxygenation. During titration of complex I activity with rotenone, progressive reduction of NAD+ to NADH was detected at >20% complex I inhibition, but substantial decreases in ATP levels and mitochondrial membrane potential did not occur until >70% inhibition. NAD+ was reduced to NADH during hypoxia, but the NADH formed was fully reoxidized during reoxygenation, consistent with the conclusion that complex I function was not limiting for recovery. Extensive degradation of cytosolic and mitochondrial NAD(H) pools occurred during either hypoxia or severe electron transport inhibition by rotenone, with patterns of metabolite accumulation consistent with catabolism by both NAD+ glycohydrolase and pyrophosphatase. This degradation was strongly blocked by alpha-ketoglutarate plus malate. The data demonstrate surprisingly little sensitivity of these cells to inhibition of complex I and high levels of resistance to development of complex I dysfunction during hypoxia-reoxygenation and indicate that events upstream of complex I are important for the energetic deficit. The work provides new insight into fundamental aspects of mitochondrial pathophysiology in proximal tubules during acute renal failure.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

LinkOut - more resources