Picazo Cecilia, Orozco Helena, Matallana Emilia, Aranda Agustín
Department of Biotechnology, Institute of Agrochemistry and Food Technology, IATA-CSIC, Paterna, Spain; Departament of Biochemistry and Molecular Biology, University of Valencia, Burjassot, Spain.
Department of Biotechnology, Institute of Agrochemistry and Food Technology, IATA-CSIC, Paterna, Spain.
PLoS One. 2015 Feb 6;10(2):e0117267. doi: 10.1371/journal.pone.0117267. eCollection 2015.
Saccharomyces cerevisiae chronological life span (CLS) is determined by a wide variety of environmental and genetic factors. Nutrient limitation without malnutrition, i.e. dietary restriction, expands CLS through the control of nutrient signaling pathways, of which TOR/Sch9 has proven to be the most relevant, particularly under nitrogen deprivation. The use of prototrophic wine yeast allows a better understanding of the role of nitrogen in longevity in natural and more demanding environments, such as grape juice fermentation. We previously showed that acetyltransferase Gcn5, a member of the SAGA complex, has opposite effects on CLS under laboratory and winemaking conditions, and is detrimental under the latter. Here we demonstrate that integrity of the SAGA complex is necessary for prolonged longevity, as its dismantling by SPT20 deletion causes a drop in CLS under both laboratory and winemaking conditions. The sch9Δ mutant is long-lived in synthetic SC medium, as expected, and the combined deletion of GCN5 partially suppresses this phenotype. However it is short-lived in grape juice, likely due to its low nitrogen/carbon ratio. Therefore, unbalance of nutrients can be more relevant for life span than total amounts of them. Deletion of RTG2, which codes for a protein associated with Gcn5 and is a component of the mitochondrial retrograde signal, and which communicates mitochondrial dysfunction to the nucleus, is detrimental under laboratory, but not under winemaking conditions, where respiration seems not so relevant for longevity. Transcription factor Rgm1 was found to be a novel CLS regulator Sch9-dependently.
酿酒酵母的时序寿命（CLS）由多种环境和遗传因素决定。在不造成营养不良的情况下限制营养，即饮食限制，通过控制营养信号通路来延长CLS，其中TOR/Sch9已被证明是最相关的，尤其是在氮剥夺条件下。使用原养型葡萄酒酵母有助于更好地理解氮在自然和要求更高的环境（如葡萄汁发酵）中对寿命的作用。我们之前表明，乙酰转移酶Gcn5是SAGA复合物的成员之一，在实验室和酿酒条件下对CLS有相反的影响，在后者条件下是有害的。在这里我们证明，SAGA复合物的完整性对于延长寿命是必要的，因为通过缺失SPT20来拆解该复合物会导致在实验室和酿酒条件下CLS下降。如预期的那样，sch9Δ突变体在合成SC培养基中寿命长，并且GCN5的联合缺失部分抑制了这种表型。然而，它在葡萄汁中寿命短，可能是由于其低氮/碳比。因此，营养物质的失衡对寿命的影响可能比其总量更重要。RTG2编码一种与Gcn5相关的蛋白质，是线粒体逆行信号的组成部分，可将线粒体功能障碍传递给细胞核，缺失RTG2在实验室条件下是有害的，但在酿酒条件下并非如此，在酿酒条件下呼吸似乎对寿命不太重要。转录因子Rgm1被发现是一种依赖Sch9的新型CLS调节因子。
