Structure of the deactive state of mammalian respiratory complex I

Complex I (NADH:ubiquinone oxidoreductase) is central to energy metabolism in mammalian mitochondria. It couples NADH oxidation by ubiquinone to proton transport across the energy-conserving inner membrane, catalyzing respiration and driving ATP synthesis. In the absence of substrates, ‘active’ complex I gradually enters a pronounced resting or ‘deactive’ state. The active-deactive transition occurs during ischemia and is crucial for controlling how respiration recovers upon reperfusion. Here, we set a highly-active preparation of Bos taurus complex I into the biochemically-defined deactive state, and used single-particle electron cryomicroscopy to determine its structure to 4.1 Å resolution. We show that the deactive state arises when critical structural elements that form the ubiquinone-binding site become disordered, and we propose reactivation is induced when substrate binding to the NADH-reduced enzyme templates their reordering. Our structure both rationalizes biochemical data on the deactive state, and offers new insights into its physiological and cellular roles.Data were recorded at the UK National Electron Bio-Imaging Centre (eBIC) at Diamond (proposal EM13581, funded by the Wellcome Trust, MRC and BBSRC) with help from Dan Clare and Alistair Siebert. This work was supported by The Medical Research Council, grant numbers U105663141 (to J.H.) and U105184322 (K.R.V. in R. Henderson's group)

Structure of mammalian respiratory complex I.

Complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the reducing potential of NADH to drive protons across the inner mitochondrial membrane. Mammalian complex I (ref. 1) contains 45 subunits, comprising 14 core subunits that house the catalytic machinery (and are conserved from bacteria to humans) and a mammalian-specific cohort of 31 supernumerary subunits. Knowledge of the structures and functions of the supernumerary subunits is fragmentary. Here we describe a 4.2-Å resolution single-particle electron cryomicroscopy structure of complex I from Bos taurus. We have located and modelled all 45 subunits, including the 31 supernumerary subunits, to provide the entire structure of the mammalian complex. Computational sorting of the particles identified different structural classes, related by subtle domain movements, which reveal conformationally dynamic regions and match biochemical descriptions of the 'active-to-de-active' enzyme transition that occurs during hypoxia. Our structures therefore provide a foundation for understanding complex I assembly and the effects of mutations that cause clinically relevant complex I dysfunctions, give insights into the structural and functional roles of the supernumerary subunits and reveal new information on the mechanism and regulation of catalysis

Proxy Measures of Fitness Suggest Coastal Fish Farms Can Act as Population Sources and Not Ecological Traps for Wild Gadoid Fish

Background: Ecological traps form when artificial structures are added to natural habitats and induce mismatches between habitat preferences and fitness consequences. Their existence in terrestrial systems has been documented, yet little evidence suggests they occur in marine environments. Coastal fish farms are widespread artificial structures in coastal ecosystems and are highly attractive to wild fish. Methodology/Principal Findings: To investigate if coastal salmon farms act as ecological traps for wild Atlantic cod (Gadus morhua) and saithe (Pollachius virens), we compared proxy measures of fitness between farm-associated fish and control fish caught distant from farms in nine locations throughout coastal Norway, the largest coastal fish farming industry in the world. Farms modified wild fish diets in both quality and quantity, thereby providing farm-associated wild fish with a strong trophic subsidy. This translated to greater somatic (saithe: 1.06–1.12 times; cod: 1.06–1.11 times) and liver condition indices (saithe: 1.4–1.8 times; cod: 2.0–2.8 times) than control fish caught distant from farms. Parasite loads of farm-associated wild fish were modified from control fish, with increased external and decreased internal parasites, however the strong effect of the trophic subsidy overrode any effects of altered loads upon condition. Conclusions and Significance: Proxy measures of fitness provided no evidence that salmon farms function as ecological traps for wild fish. We suggest fish farms may act as population sources for wild fish, provided they are protected from fishing while resident at farms to allow their increased condition to manifest as greater reproductive output.Funding was provided by the Norwegian Research Council Havet og kysten program to the CoastACE project (no: 173384)

Fish communities associated with cold-water corals vary with depth and substratum type

AbstractUnderstanding the processes that drive the distribution patterns of organisms and the scales over which these processes operate are vital when considering the effective management of species with high commercial or conservation value. In the deep sea, the importance of scleractinian cold-water corals (CWCs) to fish has been the focus of several studies but their role remains unclear. We propose this may be due to the confounding effects of multiple drivers operating over multiple spatial scales. The aims of this study were to investigate the role of CWCs in shaping fish community structure and individual species-habitat associations across four spatial scales in the NE Atlantic ranging from “regions” (separated by >500km) to “substratum types” (contiguous). Demersal fish and substratum types were quantified from three regions: Logachev Mounds, Rockall Bank and Hebrides Terrace Seamount (HTS). PERMANOVA analyses showed significant differences in community composition between all regions which were most likely caused by differences in depths. Within regions, significant variation in community composition was recorded at scales of c. 20–3500m. CWCs supported significantly different fish communities to non-CWC substrata at Rockall Bank, Logachev and the HTS. Single-species analyses using generalised linear mixed models showed that Sebastes sp. was strongly associated with CWCs at Rockall Bank and that Neocyttus helgae was more likely to occur in CWCs at the HTS. Depth had a significant effect on several other fish species. The results of this study suggest that the importance of CWCs to fish is species-specific and depends on the broader spatial context in which the substratum is found. The precautionary approach would be to assume that CWCs are important for associated fish, but must acknowledge that CWCs in different depths will not provide redundancy or replication within spatially-managed conservation networks