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Mechanism of Regulation of Cell Energy Metabolism by Mitochondrial Lipoic Acid Synthesis
Gao Ting1,2, Xu Yanhong2, Zhang Xiaoying2, Chen Zhong2*, Ye Jianping2,3*
1College of Fisheries and Life Science, Shanghai Ocean University, Shanghai 201306, China; 2Shanghai Sixth People’s Hospital East Campus, Shanghai 201306, China; 3Pennington Biomedical Research Center, Louisiana State University, Louisiana 70808, USA
Abstract: The main functions of mitochondria include catabolism and anabolism. Catabolism is wellknown as the energy conversion process for ATP production through degradation of glucose， fatty acids and amino acids. However， the study of mitochondrial anabolism is in its infancy. According to recent studies， there is a cross-talking between the catabolism and anabolism in mitochondria. New studies suggest that mammalian mitochondria is able to synthesize short-chain fatty acids， whose end-product is lipoic acid. Lipoic acid is the major substrate in the reaction of lipoylation in the post-translational modification of protein enzymes. The data from transgenic studies suggest that dysfunction of the lipoic acid synthesis pathway results in abnormal lipoylation of proteins， which leads to disorder of mitochondrial catabolism and various deficiencies including those in embryonic development， nervous system and cardiovascular system. Lipoic acid is a common antioxidant drug in clinics and widely used in the treatment of diseases of oxidative stress， but the efficacy is weak. We propose that this may be due to un-exchangeable feature of exogenous and endogenous lipoic acid， in which the exogenous is not efficient in the lipoylation reaction of catabolic enzymes. In this review， we will discuss these points in detail.
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