Kovacs Melanie, Geltinger Florian, Verwanger Thomas, Weiss Richard, Richter Klaus, Rinnerthaler Mark
Department of Biosciences, Paris-Lodron University Salzburg, Salzburg, Austria.
Front Cell Dev Biol. 2021 Nov 19;9:774985. doi: 10.3389/fcell.2021.774985. eCollection 2021.
Besides their role as a storage for neutral lipids and sterols, there is increasing evidence that lipid droplets (LDs) are involved in cellular detoxification. LDs are in close contact to a broad variety of organelles where protein- and lipid exchange is mediated. Mitochondria as a main driver of the aging process produce reactive oxygen species (ROS), which damage several cellular components. LDs as highly dynamic organelles mediate a potent detoxification mechanism by taking up toxic lipids and proteins. A stimulation of LDs induced by the simultaneously overexpression of Lro1p and Dga1p (both encoding acyltransferases) prolongs the chronological as well as the replicative lifespan of yeast cells. The increased number of LDs reduces mitochondrial fragmentation as well as mitochondrial ROS production, both phenotypes that are signs of aging. Strains with an altered LD content or morphology as in the or mutant lead to a reduced replicative lifespan. In a yeast strain defective for the LON protease Pim1p, which showed an enhanced ROS production, increased doubling time and an altered mitochondrial morphology, a overexpression resulted in a partially reversion of this "premature aging" phenotype.
除了作为中性脂质和固醇的储存库外，越来越多的证据表明脂滴（LDs）参与细胞解毒。脂滴与多种细胞器紧密接触，介导蛋白质和脂质的交换。线粒体作为衰老过程的主要驱动者会产生活性氧（ROS），其会损害多种细胞成分。脂滴作为高度动态的细胞器，通过摄取有毒脂质和蛋白质介导一种有效的解毒机制。同时过表达Lro1p和Dga1p（两者均编码酰基转移酶）诱导的脂滴刺激可延长酵母细胞的时序寿命和复制寿命。脂滴数量的增加减少了线粒体碎片化以及线粒体ROS的产生，这两种表型都是衰老的迹象。LD含量或形态改变的菌株，如在 或 突变体中，会导致复制寿命缩短。在LON蛋白酶Pim1p缺陷的酵母菌株中，该菌株表现出ROS产生增加、倍增时间延长和线粒体形态改变，过表达 会导致这种“早衰”表型部分逆转。
