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Review
. 2012:2012:696215.
doi: 10.1155/2012/696215. Epub 2012 Jan 2.

Cellular dysfunction in diabetes as maladaptive response to mitochondrial oxidative stress

Alba Naudi  1 , Mariona Jove, Victoria Ayala, Anna Cassanye, Jose Serrano, Hugo Gonzalo, Jordi Boada, Joan Prat, Manuel Portero-Otin, Reinald Pamplona
Affiliations
Review

Cellular dysfunction in diabetes as maladaptive response to mitochondrial oxidative stress

Alba Naudi et al. Exp Diabetes Res. 2012.

Abstract

Oxidative stress has been implicated in diabetes long-term complications. In this paper, we summarize the growing evidence suggesting that hyperglycemia-induced overproduction of superoxide by mitochondrial electron transport chain triggers a maladaptive response by affecting several metabolic and signaling pathways involved in the pathophysiology of cellular dysfunction and diabetic complications. In particular, it is our goal to describe physiological mechanisms underlying the mitochondrial free radical production and regulation to explain the oxidative stress derived from a high intracellular glucose concentration and the resulting maladaptive response that leads to a cellular dysfunction and pathological state. Finally, we outline potential therapies for diabetes focused to the prevention of mitochondrial oxidative damage.

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Figures

Figure 1
Figure 1
Uncoupling proteins (UCPs) respond to hyperglycemia-induced overproduction of mitochondrial superoxide by catalyzing mild uncoupling, which lowers membrane potential (ΔΨm) and decreases superoxide production by mitochondrial complex I and III of the electron transport chain. Antioxidants limit the impact of superoxide production on molecular oxidative damage (for more details, see text). MS: mitochondrial redox shuttles; O2 •−: superoxide radical; PT: pyruvate transporter; TCA: tricarboxylic acid cycle.
Figure 2
Figure 2
Hyperglycemia-induced mitochondrial free radical production induces DNA damage that activates PARP and modifies GADPH leading to a block of glycolysis (for more details, see text).
Figure 3
Figure 3
Intracellular high-glucose metabolism and oxidative stress. When intracellular glucose concentration increases in target cells of diabetes complications, it causes increased mitochondrial production of ROS and activates negative feedback loops to protect target cells from ROS-induced damage. The maladaptive response, however, leads to the activation of metabolic pathways that are involved in the diabetes vascular disfunction.
See this image and copyright information in PMC

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