Hänschke Lea, Heier Christoph, Maya Palacios Santiago José, Özek Huseyin Erdem, Thiele Christoph, Bauer Reinhard, Kühnlein Ronald P, Bülow Margret H
Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany.
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
Front Aging. 2022 Feb 14;3:800153. doi: 10.3389/fragi.2022.800153. eCollection 2022.
The human gene encodes for the enzyme lysosomal acid lipase, which hydrolyzes cholesteryl ester and triacylglycerol. Lysosomal acid lipase deficiency results in Wolman disease and cholesteryl ester storage disease. The genome encodes for two LIPA orthologs, Magro and Lipase 3. Magro is a gut lipase that hydrolyzes triacylglycerides, while Lipase 3 lacks characterization based on mutant phenotypes. We found previously that transcription is highly induced in mutants with defects in peroxisome biogenesis, but the conditions that allow a similar induction in wildtypic flies are not known. Here we show that is drastically upregulated in starved larvae and starved female flies, as well as in aged male flies. We generated a lipase 3 mutant that shows sex-specific starvation resistance and a trend to lifespan extension. Using lipidomics, we demonstrate that Lipase 3 mutants accumulate phosphatidylinositol, but neither triacylglycerol nor diacylglycerol. Our study suggests that, in contrast to its mammalian homolog LIPA, Lipase 3 is a putative phospholipase that is upregulated under extreme conditions like prolonged nutrient deprivation and aging.
人类基因编码溶酶体酸性脂肪酶,该酶可水解胆固醇酯和三酰甘油。溶酶体酸性脂肪酶缺乏会导致沃尔曼病和胆固醇酯贮积病。基因组编码两个LIPA直系同源基因,即Magro和脂肪酶3。Magro是一种可水解甘油三酯的肠道脂肪酶,而脂肪酶3缺乏基于突变体表型的特征描述。我们之前发现,在过氧化物酶体生物发生存在缺陷的突变体中,其转录被高度诱导,但在野生型果蝇中导致类似诱导的条件尚不清楚。在此我们表明,在饥饿幼虫、饥饿雌蝇以及老龄雄蝇中,其表达大幅上调。我们构建了一个脂肪酶3突变体,该突变体表现出性别特异性的饥饿抗性以及寿命延长的趋势。通过脂质组学分析,我们证明脂肪酶3突变体积累磷脂酰肌醇,但不积累甘油三酯和二酰甘油。我们的研究表明,与其哺乳动物同源物LIPA不同,脂肪酶3是一种假定的磷脂酶,在长期营养剥夺和衰老等极端条件下会上调表达。