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J. Biol. Chem., Vol. 282, Issue 26, 19217-19226, June 29, 2007

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Aging Process Modulates Nonlinear Dynamics in Liver Cell Metabolism^*

From the Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229

Regulatory dynamics of energy metabolism in living cells entails a coordinated response of multiple enzyme networks that operate under non-equilibrium conditions. Here we show that mitochondrial dysfunctions associated with the aging process significantly modify nonlinear dynamical signatures in free radical generation/removal, thereby altering energy metabolism in liver cells. We support our data with a plausible biochemical mechanism for modified bioenergetics that involves uncoupling protein-2 that is up-regulated in aged cells as an adaptive response to mitigate increased oxidative stress. Combining high spatial and temporal resolution imaging and bio-energetic measurements, our work provides experimental support to the hypothesis that mitochondria manifest nonlinear dynamical behavior for efficiently regulating energy metabolism in intact cells, and any partial or complete reduction in this behavior would contribute to organ dysfunctions including the aging process and other disease processes.

Received for publication, January 19, 2007 , and in revised form, April 17, 2007.

^* This work was supported in part by NIA, National Institutes of Health Grant 2RO1-AG007218-18A1 from (to B. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229. Tel.: 210-567-0397; Fax: 210-567-2047; E-mail: hermanb{at}uthscsa.edu.

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