Mammalian cells use a specialized and complex machinery for the removal of altered proteins or dysfunctional organelles. Such machinery is part of a mechanism called autophagy. Moreover, when autophagy is specifically employed for the removal of dysfunctional mitochondria, it is called mitophagy. Autophagy and mitophagy have important physiological implications and roles associated with cellular differentiation, resistance to stresses such as starvation, metabolic control and adaptation to the changing microenvironment. Unfortunately, transformed cancer cells often exploit autophagy and mitophagy for sustaining their metabolic reprogramming and growth to a point that autophagy and mitophagy are recognized as promising targets for ongoing and future antitumoral therapies. Sirtuins are NAD+ dependent deacylases with a fundamental role in sensing and modulating cellular response to external stresses such as nutrients availability and therefore involved in aging, oxidative stress control, inflammation, differentiation and cancer. It is clear, therefore, that autophagy, mitophagy and sirtuins share many common aspects to a point that, recently, sirtuins have been linked to the control of autophagy and mitophagy. In the context of cancer, such a control is obtained by modulating transcription of autophagy and mitophagy genes, by post translational modification of proteins belonging to the autophagy and mitophagy machinery, by controlling ROS production or major metabolic pathways such as Krebs cycle or glutamine metabolism. The present review details current knowledge on the role of sirtuins, autophagy and mitophagy in cancer to then proceed to discuss how sirtuins can control autophagy and mitophagy in cancer cells. Finally, we discuss sirtuins role in the context of tumor progression and metastasis indicating glutamine metabolism as an example of how a concerted activation and/or inhibition of sirtuins in cancer cells can control autophagy and mitophagy by impinging on the metabolism of this fundamental amino acid.

哺乳动物细胞使用一种专门且复杂的机制来去除改变的蛋白质或功能失调的细胞器。这种机制是一种称为自噬的机制的一部分。此外，当自噬专门用于去除功能失调的线粒体时，它被称为线粒体自噬。自噬和线粒体自噬具有重要的生理意义和与细胞分化、对饥饿等压力的抵抗、代谢控制和适应不断变化的微环境相关的作用。不幸的是，转化的癌细胞经常利用自噬和线粒体自噬来维持其代谢重编程和生长，以至于自噬和线粒体自噬被认为是正在进行和未来抗肿瘤治疗的有希望的目标。Sirtuins 是 NAD+ 依赖性脱酰基酶，在感知和调节细胞对外部压力（如营养物质可用性）的反应中具有重要作用，因此参与衰老、氧化应激控制、炎症、分化和癌症。因此，很明显，自噬、线粒体自噬和 sirtuins 有许多共同点，以至于最近，sirtuins 与自噬和线粒体自噬的控制有关。在癌症的背景下，这种控制是通过调节自噬和线粒体自噬基因的转录、通过对属于自噬和线粒体自噬机制的蛋白质进行翻译后修饰、通过控制 ROS 产生或主要代谢途径（如克雷布斯循环或谷氨酰胺代谢）来获得的。本综述详细介绍了目前关于sirtuins作用的知识，癌症中的自噬和线粒体自噬然后继续讨论sirtuins如何控制癌细胞中的自噬和线粒体自噬。最后，我们讨论了sirtuins在肿瘤进展和转移中的作用，表明谷氨酰胺代谢作为一个例子，说明癌细胞中sirtuins的协同激活和/或抑制如何通过影响这种基本氨基酸的代谢来控制自噬和线粒体自噬。