Izmir Institute of Technology, Department of Molecular Biology and Genetics, 35430 Urla, Izmir, Turkey.
Izmir Institute of Technology, Department of Molecular Biology and Genetics, 35430 Urla, Izmir, Turkey; Inonu University, Medical School, Department of Medical Biology and Genetics, Battalgazi, Malatya, Turkey.
Gene. 2019 Jul 20;706:172-180. doi: 10.1016/j.gene.2019.05.001. Epub 2019 May 10.
Molecular mechanisms of aging and longevity are still mostly unknown. Mitochondria play central roles in cellular metabolism and aging. In this study, we identified three deletion mutants of mitochondrial metabolism genes (ppa2∆, dss1∆, and afg3∆) that live longer than wild-type cells. These long-lived cells harbored significantly decreased amount of mitochondrial DNA (mtDNA) and reactive oxygen species (ROS). Compared to the serpentine nature of wild-type mitochondria, a different dynamics and distribution pattern of mitochondria were observed in the mutants. Both young and old long-lived cells produced relatively low but adequate levels of ATP for cellular activities. The status of the retrograde signaling was checked by expression of CIT2 gene and found activated in long-lived mutants. The mutant cells were also profiled for their gene expression patterns, and genes that were differentially regulated were determined. All long-lived cells comprised similar pleiotropic phenotype regarding mitochondrial dynamics and functions. Thus, this study suggests that DSS1, PPA2, and AFG3 genes modulate the lifespan by altering the mitochondrial morphology and functions.
衰老和长寿的分子机制在很大程度上仍然未知。线粒体在细胞代谢和衰老中起着核心作用。在这项研究中，我们鉴定了三个线粒体代谢基因（ppa2∆、dss1∆和 afg3∆）的缺失突变体，它们比野生型细胞寿命更长。这些长寿细胞的线粒体 DNA（mtDNA）和活性氧（ROS）含量明显减少。与野生型线粒体的蛇形性质相比，在突变体中观察到线粒体的不同动力学和分布模式。与野生型相比，年轻和年老的长寿细胞产生相对较低但足以满足细胞活动的 ATP 水平。通过 CIT2 基因的表达检查了逆行信号的状态，发现长寿突变体中被激活。还对突变细胞进行了基因表达谱分析，并确定了差异调节的基因。所有长寿细胞在涉及线粒体动力学和功能的多效表型方面具有相似性。因此，这项研究表明，DSS1、PPA2 和 AFG3 基因通过改变线粒体形态和功能来调节寿命。
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