Knapp-Wilson 2021 bioRxiv

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Knapp-Wilson A, Pereira GC, Buzzard E, Richardson A, Corey RA, Neal C, Verkade P, Halestrap AP, Gold VAM, Kuwabara P, Collinson I (2021) Maintenance of complex I and respiratory super-complexes by NDUF-11 is essential for respiratory function, mitochondrial structure and health in C. elegans. bioRxiv doi: https://doi.org/10.1101/2021.01.06.425530.

» bioRxiv Open Access

Knapp-Wilson Amber, Pereira Goncalo C, Buzzard Emma, Richardson Andrew, Corey Robin A, Neal Chris, Verkade Paul, Halestrap Andrew P, Gold Vicki A M, Kuwabara Patricia, Collinson Ian (2021) bioRxiv

Abstract: Mitochondrial super-complexes form around a conserved core of monomeric complex I and dimeric complex III; wherein subunit NDUFA11, of the former, is conspicuously situated at the interface. We identified B0491.5 (NDUF-11) as the C. elegans homologue, of which animals homozygous for a CRISPR-Cas9 generated knockout allele arrested at the L2 development stage. Reducing expression by RNAi allowed development to the adult stage, enabling characterisation of the consequences: destabilisation of complex I and its super-complexes, and perturbation of respiratory function. The loss of NADH-dehydrogenase activity is compensated by enhanced complex II activity, resulting in excessive detrimental ROS production. Meanwhile, electron cryo-tomography highlight aberrant cristae morphology and widening of the inter-membrane space and cristae junctions. The requirement of NDUF-11 for balanced respiration, mitochondrial morphology and development highlights the importance of complex I/ super-complex maintenance. Their perturbation by this, or other means, is likely to be the cause of metabolic stress and disease.

Keywords: Caenorhabditis elegans, Worm, Mitochondria, Respiration, Electron-transfer chain, Super-complexes, Respirasome, Mitochondrial ultrastructure, Cryo-electron tomography, NDUF-11 Bioblast editor: Plangger M O2k-Network Lab: UK Bristol Halestrap AP


Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression 


Organism: Caenorhabditis elegans 

Preparation: Isolated mitochondria  Enzyme: Supercomplex 

Coupling state: LEAK, OXPHOS  Pathway: N, S  HRR: Oxygraph-2k 

2021-01