Heinz Daniela, Krotova Evgeniia, Hamann Andrea, Osiewacz Heinz D
Institute of Molecular Biosciences, J.W. Goethe University, Frankfurt am Main, Germany.
Front Cell Dev Biol. 2021 Mar 4;9:616520. doi: 10.3389/fcell.2021.616520. eCollection 2021.
Organismic aging is known to be controlled by genetic and environmental traits. Pathways involved in the control of cellular metabolism play a crucial role. Previously, we identified a role of PaCLPP, a mitochondrial matrix protease, in the control of the mitochondrial energy metabolism, aging, and lifespan of the fungal aging model . Most surprisingly, we made the counterintuitive observation that the ablation of this component of the mitochondrial quality control network leads to lifespan extension. In the current study, we investigated the role of energy metabolism of . An age-dependent metabolome analysis of the wild type and a deletion strain verified differences and changes of various metabolites in cultures of the mutant and the wild type. Based on these data, we generated and analyzed a deletion mutant and a Δ/Δ double mutant. In both mutants PaSNF1, the catalytic α-subunit of AMP-activated protein kinase (AMPK) is ablated. PaSNF1 was found to be required for the development of fruiting bodies and ascospores and the progeny of sexual reproduction of this ascomycete and impact mitochondrial dynamics and autophagy. Most interestingly, while the single deletion mutant is characterized by a slight lifespan increase, simultaneous deletion of and leads to a pronounced lifespan extension. This synergistic effect is strongly reinforced in the presence of the mating-type "minus"-linked allele of the gene. Compared to the wild type, culture temperature of 35°C instead of the standard laboratory temperature of 27°C leads to a short-lived phenotype of the Δ/Δ double mutant. Overall, our study provides novel evidence for complex interactions of different molecular pathways involved in mitochondrial quality control, gene expression, and energy metabolism in the control of organismic aging.
已知生物体衰老受遗传和环境特征控制。参与细胞代谢调控的信号通路起着关键作用。此前，我们确定了线粒体基质蛋白酶PaCLPP在控制真菌衰老模型的线粒体能量代谢、衰老和寿命方面的作用。最令人惊讶的是，我们得出了与直觉相反的观察结果，即线粒体质量控制网络这一组成部分的缺失会导致寿命延长。在当前研究中，我们研究了……的能量代谢作用。对野生型和一个……缺失菌株进行的年龄依赖性代谢组分析证实了该突变体和野生型培养物中各种代谢物的差异和变化。基于这些数据，我们构建并分析了一个……缺失突变体和一个Δ/Δ双突变体。在这两个突变体中，AMP激活的蛋白激酶（AMPK）的催化α亚基PaSNF1被敲除。发现PaSNF1对于子实体和子囊孢子的发育以及这种子囊菌有性繁殖的后代是必需的，并且会影响线粒体动力学和自噬。最有趣的是，虽然单个……缺失突变体的特征是寿命略有增加，但同时缺失……和……会导致寿命显著延长。在存在与……基因的交配型“负链”等位基因的情况下，这种协同效应会大大增强。与野生型相比，培养温度为35°C而非标准实验室温度27°C会导致Δ/Δ双突变体出现短寿表型。总体而言，我们的研究为线粒体质量控制、基因表达和能量代谢中涉及的不同分子信号通路在控制生物体衰老方面的复杂相互作用提供了新证据。
