TargetMITO:在酵母中生成功能性合成线粒体靶向序列的规则模型
TargetMITO: a rule-based model for generating functional synthetic mitochondrial targeting sequences in yeast
TargetMITO 是一个规则驱动的计算模型,可在严格控制设计参数的前提下生成功能性合成线粒体靶向序列(MTS)。研究以芽殖酵母为对象,验证了人为将 OXPHOS 蛋白重定位到细胞核后,前体蛋白仍具有特异性的线粒体导入能力,说明存在依赖货物蛋白的功能兼容性。该工作为理解 MTS 无共有序列却决定导入特异性的机制提供了工具,并朝改进线粒体疾病的基因治疗方向推进。
来源:Nucleic Acids Research · doi.org
Mitochondria are essential organelles containing their own genomes, encoding a few proteins essential for energy production. Most of the mitochondrial proteins are nucleus-encoded, translated as precursors in the cytosol, with a large fraction of these precursors properly addressed by an N-terminal mitochondrial targeting sequence (MTS). These MTS share common features but no consensus sequence can explain their functionality nor the precursors-specific determinants of mitochondrial import. To help understand this mechanism, we created a simple computational model to generate functional synthetic MTS while maintaining a tight control on the design parameters. Using the budding yeast, we demonstrated the presence of precursors-specific import capabilities in addressing artificially nucleus-relocated OXPHOS proteins. Our research confirms the existence of cargo-dependent functional compatibilities and takes us one step closer towards improving gene therapy-based treatment of mitochondrial diseases.