Dakik Paméla, Medkour Younes, Mohammad Karamat, Titorenko Vladimir I
Department of Biology, Concordia University, Montreal, QC, Canada.
Front Physiol. 2019 Apr 18;10:461. doi: 10.3389/fphys.2019.00461. eCollection 2019.
Recent studies have revealed that some low-molecular weight molecules produced in mitochondria are essential contributing factors to aging and aging-associated pathologies in evolutionarily distant eukaryotes. These molecules are intermediates or products of certain metabolic reactions that are activated in mitochondria in response to specific changes in the nutrient, stress, proliferation, or age status of the cell. After being released from mitochondria, these metabolites directly or indirectly change activities of a distinct set of protein sensors that reside in various cellular locations outside of mitochondria. Because these protein sensors control the efficiencies of some pro- or anti-aging cellular processes, such changes in their activities allow to create a pro- or anti-aging cellular pattern. Thus, mitochondria can function as signaling platforms that respond to certain changes in cell stress and physiology by remodeling their metabolism and releasing a specific set of metabolites known as "mitobolites." These mitobolites then define the pace of cellular and organismal aging because they regulate some longevity-defining processes taking place outside of mitochondria. In this review, we discuss recent progress in understanding mechanisms underlying the ability of mitochondria to function as such signaling platforms in aging and aging-associated diseases.
最近的研究表明，线粒体中产生的一些低分子量分子是进化上距离遥远的真核生物衰老及衰老相关病理的重要促成因素。这些分子是某些代谢反应的中间体或产物，它们在线粒体中因应细胞营养、应激、增殖或年龄状态的特定变化而被激活。从线粒体释放后，这些代谢物直接或间接改变一组位于线粒体外不同细胞位置的独特蛋白质传感器的活性。由于这些蛋白质传感器控制着一些促衰老或抗衰老细胞过程的效率，它们活性的这种变化能够形成促衰老或抗衰老的细胞模式。因此，线粒体可以作为信号平台，通过重塑其代谢并释放一组特定的被称为“线粒体代谢物”的代谢物来响应细胞应激和生理的某些变化。这些线粒体代谢物随后决定细胞和机体衰老的速度，因为它们调节着发生在线粒体外的一些决定寿命的过程。在这篇综述中，我们讨论了在理解线粒体在衰老及衰老相关疾病中作为此类信号平台的能力背后机制方面的最新进展。
