bims-resufa 2021-12-19 papers

Issue of 2021–12–19
three papers selected by
Vera Strogolova, Strong Microbials, Inc

Structure. 2021 Dec 06. pii: S0969-2126(21)00420-2. [Epub ahead of print]

The respiratory supercomplex from C. glutamicum.

Agnes Moe, Terezia Kovalova, Sylwia Król, David J Yanofsky, Michael Bott, Dan Sjöstrand, John L Rubinstein, Martin Högbom, Peter Brzezinski.

Corynebacterium glutamicum is a preferentially aerobic gram-positive bacterium belonging to the phylum Actinobacteria, which also includes the pathogen Mycobacterium tuberculosis. In these bacteria, respiratory complexes III and IV form a CIII2CIV2 supercomplex that catalyzes oxidation of menaquinol and reduction of dioxygen to water. We isolated the C. glutamicum supercomplex and used cryo-EM to determine its structure at 2.9 Å resolution. The structure shows a central CIII2 dimer flanked by a CIV on two sides. A menaquinone is bound in each of the QN and QP sites in each CIII and an additional menaquinone is positioned ∼14 Å from heme bL. A di-heme cyt. cc subunit electronically connects each CIII with an adjacent CIV, with the Rieske iron-sulfur protein positioned with the iron near heme bL. Multiple subunits interact to form a convoluted sub-structure at the cytoplasmic side of the supercomplex, which defines a path for proton transfer into CIV.

Keywords: Actinobacteria; Bioenergetics; Electron transfer; cytochrome bc(1); cytochrome c oxidase; electrochemical potential; energy conservation; membrane protein; proton transfer; respiration

DOI: https://doi.org/10.1016/j.str.2021.11.008

Antioxid Redox Signal. 2021 Dec 16.

A dynamic substrate pool revealed by cryo-EM of a lipid-preserved respiratory supercomplex.

Tae Jin Jeon, Seong-Gyu Lee, Suk Hyun Yoo, Myeongbin Kim, Dabin Song, Joong Hyun Ryu, Hwangseo Park, Deok Soo Kim, Jaekyung Hyun, Ho Min Kim, Seong Eon Ryu.

AIMS: Mitochondrial respiratory supercomplexes mediate redox electron transfer, generating a proton gradient for ATP synthesis. To provide structural information on the function of supercomplexes in physiologically relevant conditions, we conducted cryo-electron microscopy studies with supercomplexes in a lipid-preserving state.
RESULTS: Here, we present cryo-electron microscopy structures of bovine respiratory supercomplex I1III2IV1 by using a lipid-preserving sample preparation. The preparation greatly enhances the inter-complex quinone transfer activity. The structures reveal large inter-complex motions that result in different shapes and sizes of the inter-complex space between complexes I and III, forming a dynamic substrate pool. Biochemical and structural analyses indicated that inter-complex phospholipids mediate the inter-complex motions. An analysis of the different classes of focus-refined complex I showed that structural switches due to quinone reduction led to the formation of a novel channel that could transfer reduced quinones to the inter-complex substrate pool. Innovation and Conclusion: Our results indicate potential mechanism for the facilitated electron transfer involving a dynamic substrate pool and inter-complex movement by which supercomplexes play an active role in the regulation of metabolic flux and reactive oxygen species.

DOI: https://doi.org/10.1089/ars.2021.0114

BMC Biol. 2021 Dec 15. 19(1): 265

Enhanced hepatic respiratory capacity and altered lipid metabolism support metabolic homeostasis during short-term hypoxic stress.

Katie A O'Brien, Ben D McNally, Alice P Sowton, Antonio Murgia, James Armitage, Luke W Thomas, Fynn N Krause, Lucas A Maddalena, Ian Francis, Stefan Kavanagh, Dominic P Williams, Margaret Ashcroft, Julian L Griffin, Jonathan J Lyon, Andrew J Murray.

BACKGROUND: Tissue hypoxia is a key feature of several endemic hepatic diseases, including alcoholic and non-alcoholic fatty liver disease, and organ failure. Hypoxia imposes a severe metabolic challenge on the liver, potentially disrupting its capacity to carry out essential functions including fuel storage and the integration of lipid metabolism at the whole-body level. Mitochondrial respiratory function is understood to be critical in mediating the hepatic hypoxic response, yet the time-dependent nature of this response and the role of the respiratory chain in this remain unclear.
RESULTS: Here, we report that hepatic respiratory capacity is enhanced following short-term exposure to hypoxia (2 days, 10% O2) and is associated with increased abundance of the respiratory chain supercomplex III2+IV and increased cardiolipin levels. Suppression of this enhanced respiratory capacity, achieved via mild inhibition of mitochondrial complex III, disrupted metabolic homeostasis. Hypoxic exposure for 2 days led to accumulation of plasma and hepatic long chain acyl-carnitines. This was observed alongside depletion of hepatic triacylglycerol species with total chain lengths of 39-53 carbons, containing palmitic, palmitoleic, stearic, and oleic acids, which are associated with de novo lipogenesis. The changes to hepatic respiratory capacity and lipid metabolism following 2 days hypoxic exposure were transient, becoming resolved after 14 days in line with systemic acclimation to hypoxia and elevated circulating haemoglobin concentrations.
CONCLUSIONS: The liver maintains metabolic homeostasis in response to shorter term hypoxic exposure through transient enhancement of respiratory chain capacity and alterations to lipid metabolism. These findings may have implications in understanding and treating hepatic pathologies associated with hypoxia.

Keywords: De novo lipogenesis; Hepatic mitochondria; Hypoxia; Mitochondrial respiratory chain; Mitochondrial supercomplexes

DOI: https://doi.org/10.1186/s12915-021-01192-0