Department of Biological, Geological and Environmental Sciences, University of Catania, Via S. Sofia 64, 95125 Catania, Italy.
we.MitoBiotech S.R.L., C.so Italia 174, 95125 Catania, Italy.
Int J Mol Sci. 2023 Feb 12;24(4):3687. doi: 10.3390/ijms24043687.
Voltage-Dependent Anion-selective Channel isoform 1 (VDAC1) is the most abundant isoform of the outer mitochondrial membrane (OMM) porins and the principal gate for ions and metabolites to and from the organelle. VDAC1 is also involved in a number of additional functions, such as the regulation of apoptosis. Although the protein is not directly involved in mitochondrial respiration, its deletion in yeast triggers a complete rewiring of the whole cell metabolism, with the inactivation of the main mitochondrial functions. In this work, we analyzed in detail the impact of VDAC1 knockout on mitochondrial respiration in the near-haploid human cell line HAP1. Results indicate that, despite the presence of other VDAC isoforms in the cell, the inactivation of VDAC1 correlates with a dramatic impairment in oxygen consumption and a re-organization of the relative contributions of the electron transport chain (ETC) enzymes. Precisely, in VDAC1 knockout HAP1 cells, the complex I-linked respiration (N-pathway) is increased by drawing resources from respiratory reserves. Overall, the data reported here strengthen the key role of VDAC1 as a general regulator of mitochondrial metabolism.
电压依赖性阴离子选择性通道 1 型（VDAC1）是外线粒体膜（OMM）孔道中最丰富的同工型，也是细胞器内外离子和代谢物的主要门户。VDAC1 还参与许多其他功能，如细胞凋亡的调节。尽管该蛋白不直接参与线粒体呼吸，但在酵母中缺失它会引发整个细胞代谢的完全重新布线，导致主要线粒体功能失活。在这项工作中，我们详细分析了 VDAC1 敲除对近单倍体人细胞系 HAP1 中线粒体呼吸的影响。结果表明，尽管细胞中存在其他 VDAC 同工型，但 VDAC1 的失活与耗氧量的急剧下降和电子传递链（ETC）酶的相对贡献的重新组织相关。确切地说，在 VDAC1 敲除的 HAP1 细胞中，通过从呼吸储备中汲取资源，I 型复合物连接的呼吸（N 途径）增加。总的来说，这里报道的数据加强了 VDAC1 作为线粒体代谢通用调节剂的关键作用。
