Reina Simona, Pittalà Maria Gaetana Giovanna, Guarino Francesca, Messina Angela, De Pinto Vito, Foti Salvatore, Saletti Rosaria
Section of Molecular Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
Section of Biology and Genetics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
Front Cell Dev Biol. 2020 Jun 4;8:397. doi: 10.3389/fcell.2020.00397. eCollection 2020.
Cysteine residues are reactive amino acids that can undergo several modifications driven by redox reagents. Mitochondria are the source of an abundant production of radical species, and it is surprising that such a large availability of highly reactive chemicals is compatible with viable and active organelles, needed for the cell functions. In this work, we review the results highlighting the modifications of cysteines in the most abundant proteins of the outer mitochondrial membrane (OMM), that is, the voltage-dependent anion selective channel (VDAC) isoforms. This interesting protein family carries several cysteines exposed to the oxidative intermembrane space (IMS). Through mass spectrometry (MS) analysis, cysteine posttranslational modifications (PTMs) were precisely determined, and it was discovered that such cysteines can be subject to several oxidization degrees, ranging from the disulfide bridge to the most oxidized, the sulfonic acid, one. The large spectra of VDAC cysteine oxidations, which is unique for OMM proteins, indicate that they have both a regulative function and a buffering capacity able to counteract excess of mitochondrial reactive oxygen species (ROS) load. The consequence of these peculiar cysteine PTMs is discussed.
半胱氨酸残基是具有反应活性的氨基酸，可经历由氧化还原试剂驱动的多种修饰。线粒体是大量自由基产生的来源，令人惊讶的是，如此大量高活性化学物质的存在竟然与细胞功能所需的存活且活跃的细胞器相容。在这项工作中，我们回顾了突出线粒体外膜（OMM）最丰富蛋白质中半胱氨酸修饰的结果，即电压依赖性阴离子选择性通道（VDAC）亚型。这个有趣的蛋白质家族有几个半胱氨酸暴露于氧化的膜间隙（IMS）。通过质谱（MS）分析，精确确定了半胱氨酸的翻译后修饰（PTM），并且发现这些半胱氨酸可以经历多种氧化程度，从二硫键到氧化程度最高的磺酸。VDAC半胱氨酸氧化的广泛谱图是OMM蛋白所特有的，表明它们既具有调节功能又具有缓冲能力，能够抵消过量的线粒体活性氧（ROS）负荷。讨论了这些特殊半胱氨酸PTM的后果。
