半胱氨酸毒性通过改变铁稳态来引起与年龄相关的线粒体衰退，这一成果由美国犹他大学医学院的Adam L. Hughes小组近日报道。相关论文2020年1月23日发表在《细胞》上。

在酵母中，研究人员表明溶酶体样液泡通过空间上划分氨基酸来维持线粒体呼吸。液泡功能的缺陷导致细胞内氨基酸稳态的破坏，从而导致与年龄有关的线粒体衰老。在氨基酸中，研究人员发现半胱氨酸对线粒体毒性最大，并表明非液泡半胱氨酸的升高通过氧化剂机制来限制了细胞内铁的可用性，从而损害线粒体呼吸。半胱氨酸的消耗或铁的补充可恢复液泡受损细胞的线粒体健康，并防止衰老过程中的线粒体衰退。这些结果表明，半胱氨酸毒性是年龄相关线粒体退化的主要驱动因素，并将液泡的氨基酸区隔鉴定为最小化氨基酸毒性的细胞策略。

Title: Cysteine Toxicity Drives Age-Related Mitochondrial Decline by Altering Iron Homeostasis

Author: Casey E. Hughes, Troy K. Coody, Mi-Young Jeong, Jordan A. Berg, Dennis R. Winge, Adam L. Hughes

Issue&Volume: 2020/01/23

Abstract: Mitochondria and lysosomes are functionally linked, and their interdependent declineis a hallmark of aging and disease. Despite the long-standing connection between theseorganelles, the function(s) of lysosomes required to sustain mitochondrial healthremains unclear. Here, working in yeast, we show that the lysosome-like vacuole maintainsmitochondrial respiration by spatially compartmentalizing amino acids. Defects invacuole function result in a breakdown in intracellular amino acid homeostasis, whichdrives age-related mitochondrial decline. Among amino acids, we find that cysteineis most toxic for mitochondria and show that elevated non-vacuolar cysteine impairsmitochondrial respiration by limiting intracellular iron availability through an oxidant-basedmechanism. Cysteine depletion or iron supplementation restores mitochondrial healthin vacuole-impaired cells and prevents mitochondrial decline during aging. These resultsdemonstrate that cysteine toxicity is a major driver of age-related mitochondrialdeterioration and identify vacuolar amino acid compartmentation as a cellular strategyto minimize amino acid toxicity.

DOI: 10.1016/j.cell.2019.12.035

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31397-2