bims-cytox1 2023-09-03 papers

Issue of 2023‒09‒03
two papers selected by
Gavin McStay, Liverpool John Moores University

Cell Metab. 2023 Aug 22. pii: S1550-4131(23)00289-9. [Epub ahead of print]

Preserved respiratory chain capacity and physiology in mice with profoundly reduced levels of mitochondrial respirasomes.

Dusanka Milenkovic, Jelena Misic, Johannes F Hevler, Thibaut Molinié, Injae Chung, Ilian Atanassov, Xinping Li, Roberta Filograna, Andrea Mesaros, Arnaud Mourier, Albert J R Heck, Judy Hirst, Nils-Göran Larsson.

The mammalian respiratory chain complexes I, III2, and IV (CI, CIII2, and CIV) are critical for cellular bioenergetics and form a stable assembly, the respirasome (CI-CIII2-CIV), that is biochemically and structurally well documented. The role of the respirasome in bioenergetics and the regulation of metabolism is subject to intense debate and is difficult to study because the individual respiratory chain complexes coexist together with high levels of respirasomes. To critically investigate the in vivo role of the respirasome, we generated homozygous knockin mice that have normal levels of respiratory chain complexes but profoundly decreased levels of respirasomes. Surprisingly, the mutant mice are healthy, with preserved respiratory chain capacity and normal exercise performance. Our findings show that high levels of respirasomes are dispensable for maintaining bioenergetics and physiology in mice but raise questions about their alternate functions, such as those relating to the regulation of protein stability and prevention of age-associated protein aggregation.

Keywords: OXPHOS; mitochondria; mitochondrial respirasomes; supercomplexes

DOI: https://doi.org/10.1016/j.cmet.2023.07.015

Biochim Biophys Acta Mol Basis Dis. 2023 Aug 26. pii: S0925-4439(23)00222-3. [Epub ahead of print] 166856

Mutation on MT-CO2 gene induces mitochondrial disease associated with neurodegeneration and intracerebral iron accumulation (NBIA).

Sarah Courtois, Chloé Angelini, Christelle M Durand, Nivea Dias Amoedo, Armelle Courreges, Elodie Dumon, Mégane Le Quang, Cyril Goizet, Marie-Laure Martin-Negrier, Rodrigue Rossignol, Didier Lacombe, Isabelle Coupry, Aurélien Trimouille.

Mitochondrial diseases are genetic disorders impairing mitochondrial functions. Here we describe a patient with a neurodegenerative condition associated with myopia, bilateral sensorineural hearing loss and motor disorders. Brain MRIs showed major cortico-subcortical and infra-tentorial atrophies, as well as intracerebral iron accumulation and central calcifications, compatible with a NBIA-like phenotype. Mitochondrial DNA analysis revealed an undescribed variant: m.8091G>A in the MT-CO2 gene, associated with a complex IV deficiency and a decrease of the mitochondrial respiratory chain capabilities. We report here this pathogenic variant, associated with a NBIA-like phenotype.

Keywords: Complex IV; MT-CO2; Mitochondriopathies; NBIA; iron accumulation

DOI: https://doi.org/10.1016/j.bbadis.2023.166856