1. Maintenance of complex I and its supercomplexes by NDUF-11 is essential for mitochondrial structure, function and health.
- Author
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Knapp-Wilson, Amber, Pereira, Gonçalo C., Buzzard, Emma, Ford, Holly C., Richardson, Andrew, Corey, Robin A., Neal, Chris, Verkade, Paul, Halestrap, Andrew P., Gold, Vicki A. M., Kuwabara, Patricia E., and Collinson, Ian
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MITOCHONDRIA , *NADH dehydrogenase , *REACTIVE oxygen species , *CAENORHABDITIS elegans - Abstract
Mitochondrial supercomplexes form around a conserved core of monomeric complex I and dimeric complex III; wherein a subunit of the former, NDUFA11, is conspicuously situated at the interface. We identified nduf-11 (B0491.5) as encoding the Caenorhabditis elegans homologue of NDUFA11. Animals homozygous for a CRISPR-Cas9-generated knockout allele of nduf-11 arrested at the second larval (L2) development stage. Reducing (but not eliminating) expression using RNAi allowed development to adulthood, enabling characterisation of the consequences: destabilisation of complex I and its supercomplexes and perturbation of respiratory function. The loss of NADH dehydrogenase activity was compensated by enhanced complex II activity, with the potential for detrimental reactive oxygen species (ROS) production. Cryo-electron tomography highlighted aberrant morphology of cristae and widening of both cristae junctions and the intermembrane space. The requirement of NDUF-11 for balanced respiration, mitochondrial morphology and development presumably arises due to its involvement in complex I and supercomplex maintenance. This highlights the importance of respiratory complex integrity for health and the potential for its perturbation to cause mitochondrial disease. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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