Center for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2191-7. doi: 10.1152/ajpheart.00199.2011. Epub 2011 Oct 7.
Studies to quantify the protein acetylome show that lysine-residue acetylation rivals phosphorylation in prevalence as a posttranslational modification. Interesting, this posttranslational modification is modified by nutrient flux and by redox stress and targets the vast majority of metabolic pathway proteins in the mitochondria. Furthermore, the mitochondrial deacetylase enzyme SIRT3 appears to be regulated by exercise in skeletal muscle and in response to pressure overload in the heart. The alteration of protein lysine residues by acetylation and the enzymes controlling deacetylation are beginning to be explored as important regulatory events in the control of mitochondrial function and homeostasis. This review focuses on the mitochondrial targets of SIRT3 that are functionally implicated in heart biology and pathology and on the direct cardiac consequences of the genetic manipulation of SIRT3. As therapeutic modulators of other SIRT isoforms have been identified, the longer-term objective of our understanding of this biology would be to identify SIRT3 modulators as putative cardiac therapeutic agents.
研究表明，定量蛋白质乙酰化组表明，赖氨酸残基乙酰化在作为翻译后修饰的普遍性方面可与磷酸化媲美。有趣的是，这种翻译后修饰受营养物质通量和氧化还原应激的调节，并靶向线粒体中绝大多数代谢途径蛋白。此外，线粒体脱乙酰酶 SIRT3 似乎受骨骼肌运动和心脏压力超负荷的调节。通过乙酰化和控制脱乙酰化的酶来改变蛋白质赖氨酸残基，正在被探索作为控制线粒体功能和动态平衡的重要调节事件。这篇综述重点介绍了 SIRT3 的线粒体靶标，这些靶标在心脏生物学和病理学中具有功能意义，以及 SIRT3 的遗传操作的直接心脏后果。随着其他 SIRT 同工型的治疗调节剂的鉴定，我们对这种生物学的长期目标将是鉴定 SIRT3 调节剂作为潜在的心脏治疗剂。
