Department of Molecular Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland.
Department of Molecular Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland.
Free Radic Biol Med. 2021 Feb 1;163:243-254. doi: 10.1016/j.freeradbiomed.2020.12.019. Epub 2020 Dec 19.
Cytochrome bc, also known as mitochondrial complex III, is considered to be one of the important producers of reactive oxygen species (ROS) in living organisms. Under physiological conditions, a certain level of ROS produced by mitochondrial electron transport chain (ETC) might be beneficial and take part in cellular signaling. However, elevated levels of ROS might exhibit negative effects, resulting in cellular damage. It is well known that inhibiting the electron flow within mitochondrial complex III leads to high production of ROS. However, superoxide production by cytochrome bc in a non-inhibited system remained controversial. Here, we propose a novel method for ROS detection in ETC hybrid system in solution comprising bacterial cytochrome bc and mitochondrial complex IV. We clearly show that non-inhibited cytochrome bc generates ROS and that adaptive and pathogenic mitochondrial mutations suppress and enhance ROS production, respectively. We also noted that cytochrome bc produces ROS in a rate-dependent manner and that the mechanism of ROS generation changes according to the rate of operation of the enzyme. This dependency has not yet been reported, but seems to be crucial when discussing ROS signaling originating from mitochondria.
细胞色素 bc，又称线粒体复合物 III，被认为是生物体内活性氧 (ROS) 的重要产生者之一。在生理条件下，线粒体电子传递链 (ETC) 产生的一定水平的 ROS 可能是有益的，并参与细胞信号转导。然而，ROS 水平的升高可能会产生负面影响，导致细胞损伤。众所周知，抑制线粒体复合物 III 内的电子流会导致 ROS 的大量产生。然而，非抑制系统中细胞色素 bc 产生超氧化物的情况仍存在争议。在这里，我们提出了一种在包含细菌细胞色素 bc 和线粒体复合物 IV 的溶液中检测 ETC 混合系统中 ROS 的新方法。我们清楚地表明，非抑制的细胞色素 bc 会产生 ROS，适应性和致病性的线粒体突变分别抑制和增强 ROS 的产生。我们还注意到，细胞色素 bc 以速率依赖的方式产生 ROS，并且 ROS 产生的机制根据酶的工作速率而变化。这种依赖性尚未被报道，但在讨论源自线粒体的 ROS 信号转导时似乎至关重要。
