Perico Luca, Morigi Marina, Benigni Ariela
IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Anna Maria Astori Centre, Kilometro Rosso Science and Technology Park, Bergamo, Italy.
Nephron. 2016;134(1):14-9. doi: 10.1159/000444370. Epub 2016 Jul 1.
Mitochondria are dynamic organelles whose functions are tightly regulated at multiple levels to maintain proper cellular homeostasis. Mitochondrial Sirtuin 3 (SIRT3), which belongs to an evolutionary conserved family of NAD+-dependent deacetylases, is a key regulator of the mitochondrial respiratory chain, ATP production, and fatty acid β-oxidation, and it exerts an antioxidant activity. Changes in SIRT3 expression are critical in the pathophysiology of several diseases, such as metabolic syndrome, diabetes, cancer, and aging. In experimental acute kidney injury (AKI), impairment of renal function and development of tubular injury are associated with SIRT3 reduction and mitochondrial dysfunction in proximal tubuli. SIRT3-deficient mice are more susceptible to AKI and die. Pharmacological manipulations able to increase SIRT3 preserve mitochondrial integrity, markedly limit renal injury, and accelerate functional recovery. This review highlights all the selective rescue mechanisms that point to the key role of SIRT3 as a new therapeutic target for curing renal diseases.
线粒体是动态细胞器，其功能在多个层面受到严格调控以维持适当的细胞稳态。线粒体沉默调节蛋白3（SIRT3）属于进化保守的NAD+依赖性脱乙酰酶家族，是线粒体呼吸链、ATP生成和脂肪酸β氧化的关键调节因子，并具有抗氧化活性。SIRT3表达的变化在多种疾病的病理生理学中至关重要，如代谢综合征、糖尿病、癌症和衰老。在实验性急性肾损伤（AKI）中，肾功能损害和肾小管损伤的发生与近端肾小管中SIRT3减少和线粒体功能障碍有关。SIRT3缺陷小鼠对AKI更易感且会死亡。能够增加SIRT3的药理学操作可维持线粒体完整性，显著限制肾损伤，并加速功能恢复。本综述强调了所有选择性挽救机制，这些机制表明SIRT3作为治疗肾脏疾病的新治疗靶点具有关键作用。
