Department of Psychiatry, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, 10032, USA; New York State Psychiatric Institute, New York, NY, 10032, USA.
Department of Psychology, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
Psychoneuroendocrinology. 2019 Aug;106:268-276. doi: 10.1016/j.psyneuen.2019.03.026. Epub 2019 Mar 28.
Intrinsic biological mechanisms transduce psychological stress into physiological adaptation that requires energy, but the role of mitochondria and mitochondrial DNA (mtDNA) in this process has not been defined in humans. Here, we show that similar to physical injury, exposure to psychological stress increases serum circulating cell-free mtDNA (ccf-mtDNA) levels. Healthy midlife adults exposed on two separate occasions to a brief psychological challenge exhibited a 2-3-fold increase in ccf-mtDNA, with no change in ccf-nuclear DNA levels, establishing the magnitude and specificity for ccf-mtDNA reactivity. In cell-based studies, we show that glucocorticoid signaling - a consequence of psychological stress in humans - is sufficient to induce mtDNA extrusion in a time frame consistent with stress-induced ccf-mtDNA increase. Collectively, these findings provide evidence that acute psychological stress induces ccf-mtDNA and implicate neuroendocrine signaling as a potential trigger for ccf-mtDNA release. Further controlled work is needed to confirm that observed increases in ccf-mtDNA result from stress exposure and to determine the functional significance of this effect.
内在的生物学机制将心理压力转化为生理适应，这需要能量，但线粒体和线粒体 DNA（mtDNA）在这个过程中的作用在人类中尚未确定。在这里，我们表明，类似于身体损伤，暴露于心理压力会增加血清循环无细胞 mtDNA（ccf-mtDNA）水平。健康的中年成年人在两次不同的短暂心理挑战中暴露，ccf-mtDNA 增加了 2-3 倍，而 ccf-核 DNA 水平没有变化，这就确定了 ccf-mtDNA 反应的幅度和特异性。在基于细胞的研究中，我们表明，糖皮质激素信号转导——人类心理压力的结果——足以在与应激诱导的 ccf-mtDNA 增加一致的时间范围内诱导 mtDNA 外排。总之，这些发现提供了证据表明急性心理压力会诱导 ccf-mtDNA，并暗示神经内分泌信号可能是 ccf-mtDNA 释放的潜在触发因素。需要进一步的对照研究来确认观察到的 ccf-mtDNA 增加是由于应激暴露引起的，并确定这种效应的功能意义。
