Interplay between NADH oxidation by complex I, glutathione redox state and sirtuin-3, and its role in the development of insulin resistance

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1866

Review

Cortes-Rojo, Christian¹  Alejandro Vargas-Vargas, Manuel¹  Eridani Olmos-Orizaba, Berenice¹  Raimundo Rodriguez-Orozco, Alain²  Calderon-Cortes, Elizabeth³ 

[1] Univ Michoacana, Inst Invest Quim Biol, Morelia 58030, Michoacan, Mexico

[2] Univ Michoacana, Fac Ciencias Med & Biol Dr Ignacio Chavez, Morelia 58020, Michoacan, Mexico

[3] Univ Michoacana, Fac Enfermeria, Morelia 58260, Michoacan, Mexico

关键词: Diabetes;    Obesity;    Lipid peroxidation;    Mitochondria;    Liver;    Skeletal muscle;   

DOI  :  10.1016/j.bbadis.2020.165801

来源: Elsevier

【 摘 要 】

Metabolic diseases are characterized by high NADH/NAD(+) ratios due to excessive electron supply, causing defective mitochondrial function and impaired sirtuin-3 (SIRT-3) activity, the latter driving to oxidative stress and altered fatty acid beta-oxidation. NADH is oxidized by the complex I in the electron transport chain, thereby factors inhibiting complex I like acetylation, cardiolipin peroxidation, and glutathionylation by low GSH/GSSG ratios affects SIRT3 function by increasing the NADH/NAD(+) ratio. In this review, we summarized the evidence supporting a role of the above events in the development of insulin resistance, which is relevant in the patho-genesis of obesity and diabetes. We propose that maintenance of proper NADH/NAD(+) and GSH/GSSG ratios are central to ameliorate insulin resistance, as alterations in these redox couples lead to complex I dysfunction, disruption of SIRT-3 activity, ROS production and impaired beta-oxidation, the latter two being key effectors of insulin resistance.

【 授权许可】

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