Department of Genetics, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3781-6. doi: 10.1073/pnas.1400705111. Epub 2014 Feb 20.
Mitochondrial defects underlie a multitude of human diseases. Genetic manipulation of mitochondrial regulatory pathways represents a potential therapeutic approach. We have carried out a high-throughput overexpression screen for genes that affect mitochondrial abundance or activity using flow-cytometry-based enrichment of a cell population expressing a high-complexity, concentration-normalized pool of human ORFs. The screen identified 94 candidate mitochondrial regulators including the nuclear protein GLTSCR2, also known as PICT1. GLTSCR2 enhances mitochondrial function and is required for the maintenance of oxygen consumption, consistent with a pivotal role in the control of cellular respiration. RNAi inactivation of the Caenorhabditis elegans ortholog of GLTSCR2 reduces respiration in worms, indicating functional conservation across species. GLTSCR2 controls cellular proliferation and metabolism via the transcription factor Myc, and is induced by mitochondrial stress, suggesting it may constitute a significant component of the mitochondrial signaling pathway.
线粒体缺陷是多种人类疾病的基础。对线粒体调节途径进行基因操作代表了一种有潜力的治疗方法。我们使用基于流式细胞术的方法，对表达高复杂度、浓度归一化的人 ORF 池的细胞群进行富集，进行了高通量过表达筛选，以寻找影响线粒体丰度或活性的基因。该筛选鉴定出 94 种候选线粒体调节剂，包括核蛋白 GLTSCR2，也称为 PICT1。GLTSCR2 增强线粒体功能，并且是维持耗氧量所必需的，这与它在控制细胞呼吸中的关键作用一致。用 RNAi 使秀丽隐杆线虫中 GLTSCR2 的同源物失活会降低蠕虫的呼吸作用，表明跨物种的功能保守性。GLTSCR2 通过转录因子 Myc 控制细胞增殖和代谢，并且受到线粒体应激的诱导，这表明它可能构成线粒体信号通路的重要组成部分。
