FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2520656712> ?p ?o ?g. }

• W2520656712 endingPage "126" @default.
• W2520656712 startingPage "123" @default.
• W2520656712 abstract "Gene-editing technology and large-scale proteomics are used to provide insights into the modular assembly of the human mitochondrial respiratory chain complex I, as well as identifying new assembly factors. Respiratory chain complexes, including complex I, generate the cellular energy molecule ATP, and their dysfunction is associated with various disorders including Parkinson's disease and ageing. As well as the 14 core subunits that are essential for its enzymatic function, human complex I carries 30 accessory subunits, which are actively added to the core subunits by assembly factors. Combining genome-editing technology with large-scale proteomics, Michael Ryan and colleagues study the requirement for the different accessory subunits in human cells. Their data provide insights into the modular assembly of complex I as well as identifying new assembly factors. Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes1. Complex I exists in supercomplex forms with respiratory chain complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP2. Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson’s disease and ageing3,4,5. Bacterial and human complex I share 14 core subunits that are essential for enzymatic function; however, the role and necessity of the remaining 31 human accessory subunits is unclear1,6. The incorporation of accessory subunits into the complex increases the cellular energetic cost and has necessitated the involvement of numerous assembly factors for complex I biogenesis. Here we use gene editing to generate human knockout cell lines for each accessory subunit. We show that 25 subunits are strictly required for assembly of a functional complex and 1 subunit is essential for cell viability. Quantitative proteomic analysis of cell lines revealed that loss of each subunit affects the stability of other subunits residing in the same structural module. Analysis of proteomic changes after the loss of specific modules revealed that ATP5SL and DMAC1 are required for assembly of the distal portion of the complex I membrane arm. Our results demonstrate the broad importance of accessory subunits in the structure and function of human complex I. Coupling gene-editing technology with proteomics represents a powerful tool for dissecting large multi-subunit complexes and enables the study of complex dysfunction at a cellular level." @default.
• W2520656712 created "2016-09-23" @default.
• W2520656712 creator A5006817516 @default.
• W2520656712 creator A5008757395 @default.
• W2520656712 creator A5013708479 @default.
• W2520656712 creator A5020320687 @default.
• W2520656712 creator A5047836141 @default.
• W2520656712 creator A5069235674 @default.
• W2520656712 creator A5073246906 @default.
• W2520656712 creator A5076160885 @default.
• W2520656712 creator A5076790544 @default.
• W2520656712 creator A5082096236 @default.
• W2520656712 creator A5084933832 @default.
• W2520656712 creator A5091080801 @default.
• W2520656712 date "2016-09-14" @default.
• W2520656712 modified "2023-10-16" @default.
• W2520656712 title "Accessory subunits are integral for assembly and function of human mitochondrial complex I" @default.
• W2520656712 cites W1480113445 @default.
• W2520656712 cites W1521381364 @default.
• W2520656712 cites W1523656947 @default.
• W2520656712 cites W1611787727 @default.
• W2520656712 cites W182337363 @default.
• W2520656712 cites W1849053218 @default.
• W2520656712 cites W1965285497 @default.
• W2520656712 cites W1971211089 @default.
• W2520656712 cites W1972399884 @default.
• W2520656712 cites W1973180473 @default.
• W2520656712 cites W1973925468 @default.
• W2520656712 cites W1975085160 @default.
• W2520656712 cites W1976210582 @default.
• W2520656712 cites W1977709885 @default.
• W2520656712 cites W1978680299 @default.
• W2520656712 cites W1986248905 @default.
• W2520656712 cites W1987296005 @default.
• W2520656712 cites W1998200498 @default.
• W2520656712 cites W2006659499 @default.
• W2520656712 cites W2009503896 @default.
• W2520656712 cites W2015476639 @default.
• W2520656712 cites W2016680661 @default.
• W2520656712 cites W2020432830 @default.
• W2520656712 cites W2022321112 @default.
• W2520656712 cites W2030760120 @default.
• W2520656712 cites W2032669752 @default.
• W2520656712 cites W2033507589 @default.
• W2520656712 cites W2036321220 @default.
• W2520656712 cites W2045857306 @default.
• W2520656712 cites W2057194569 @default.
• W2520656712 cites W2058570690 @default.
• W2520656712 cites W2059041864 @default.
• W2520656712 cites W2065979657 @default.
• W2520656712 cites W2068119233 @default.
• W2520656712 cites W2079394317 @default.
• W2520656712 cites W2080752012 @default.
• W2520656712 cites W2093205341 @default.
• W2520656712 cites W2097948046 @default.
• W2520656712 cites W2099540110 @default.
• W2520656712 cites W2101117598 @default.
• W2520656712 cites W2101502897 @default.
• W2520656712 cites W2102774255 @default.
• W2520656712 cites W2105388322 @default.
• W2520656712 cites W2105775411 @default.
• W2520656712 cites W2116650193 @default.
• W2520656712 cites W2117140251 @default.
• W2520656712 cites W2123878025 @default.
• W2520656712 cites W2124867628 @default.
• W2520656712 cites W2126777939 @default.
• W2520656712 cites W2132803022 @default.
• W2520656712 cites W2134822049 @default.
• W2520656712 cites W2137209165 @default.
• W2520656712 cites W2137499573 @default.
• W2520656712 cites W2157205823 @default.
• W2520656712 cites W2157809244 @default.
• W2520656712 cites W2161030070 @default.
• W2520656712 cites W2163936581 @default.
• W2520656712 cites W2164811961 @default.
• W2520656712 cites W2165012926 @default.
• W2520656712 cites W2165918134 @default.
• W2520656712 cites W2180760460 @default.
• W2520656712 cites W2278896297 @default.
• W2520656712 cites W2333034303 @default.
• W2520656712 cites W2345884405 @default.
• W2520656712 cites W2474866772 @default.
• W2520656712 cites W2512187837 @default.
• W2520656712 cites W4294107304 @default.
• W2520656712 doi "https://doi.org/10.1038/nature19754" @default.
• W2520656712 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27626371" @default.
• W2520656712 hasPublicationYear "2016" @default.
• W2520656712 type Work @default.
• W2520656712 sameAs 2520656712 @default.
• W2520656712 citedByCount "377" @default.
• W2520656712 countsByYear W25206567122016 @default.
• W2520656712 countsByYear W25206567122017 @default.
• W2520656712 countsByYear W25206567122018 @default.
• W2520656712 countsByYear W25206567122019 @default.
• W2520656712 countsByYear W25206567122020 @default.
• W2520656712 countsByYear W25206567122021 @default.
• W2520656712 countsByYear W25206567122022 @default.
• W2520656712 countsByYear W25206567122023 @default.

• next