Lopez-Fabuel Irene, Le Douce Juliette, Logan Angela, James Andrew M, Bonvento Gilles, Murphy Michael P, Almeida Angeles, Bolaños Juan P
Institute of Functional Biology and Genomics, University of Salamanca-Consejo Superior de Investigaciones Cientificas, 37007 Salamanca, Spain.
Commissariat à l'Energie Atomique et aux Energies Alternatives, Département des Sciences du Vivant, Institut d'Imagerie Biomédicale, Molecular Imaging Center, CNRS UMR 9199, Université Paris-Sud, Université Paris-Saclay, F-92260 Fontenay-aux-Roses, France.
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):13063-13068. doi: 10.1073/pnas.1613701113. Epub 2016 Oct 31.
Neurons depend on oxidative phosphorylation for energy generation, whereas astrocytes do not, a distinctive feature that is essential for neurotransmission and neuronal survival. However, any link between these metabolic differences and the structural organization of the mitochondrial respiratory chain is unknown. Here, we investigated this issue and found that, in neurons, mitochondrial complex I is predominantly assembled into supercomplexes, whereas in astrocytes the abundance of free complex I is higher. The presence of free complex I in astrocytes correlates with the severalfold higher reactive oxygen species (ROS) production by astrocytes compared with neurons. Using a complexomics approach, we found that the complex I subunit NDUFS1 was more abundant in neurons than in astrocytes. Interestingly, NDUFS1 knockdown in neurons decreased the association of complex I into supercomplexes, leading to impaired oxygen consumption and increased mitochondrial ROS. Conversely, overexpression of NDUFS1 in astrocytes promoted complex I incorporation into supercomplexes, decreasing ROS. Thus, complex I assembly into supercomplexes regulates ROS production and may contribute to the bioenergetic differences between neurons and astrocytes.
神经元依靠氧化磷酸化来产生能量，而星形胶质细胞则不然，这一独特特征对于神经传递和神经元存活至关重要。然而，这些代谢差异与线粒体呼吸链的结构组织之间的任何联系尚不清楚。在这里，我们研究了这个问题，发现神经元中的线粒体复合物I主要组装成超复合物，而在星形胶质细胞中，游离复合物I的丰度更高。星形胶质细胞中游离复合物I的存在与星形胶质细胞相比神经元产生的活性氧（ROS）高出几倍相关。使用复合物组学方法，我们发现复合物I亚基NDUFS1在神经元中比在星形胶质细胞中更丰富。有趣的是，神经元中NDUFS1的敲低减少了复合物I与超复合物的结合，导致氧消耗受损和线粒体ROS增加。相反，星形胶质细胞中NDUFS1的过表达促进了复合物I并入超复合物，减少了ROS。因此，复合物I组装成超复合物调节ROS的产生，并可能导致神经元和星形胶质细胞之间的生物能量差异。
