bims-cytox1 2023-08-27 papers

Issue of 2023‒08‒27
two papers selected by
Gavin McStay, Liverpool John Moores University

Life Sci Alliance. 2023 Nov;pii: e202301965. [Epub ahead of print]6(11):

Allotopic expression of COX6 elucidates Atco-driven co-assembly of cytochrome oxidase and ATP synthase.

Leticia Veloso R Franco, Chen-Hsien Su, Lorisa Simas Teixeira, Jhulia Almeida Clarck Chagas, Mario Henrique Barros, Alexander Tzagoloff.

The Cox6 subunit of Saccharomyces cerevisiae cytochrome oxidase (COX) and the Atp9 subunit of the ATP synthase are encoded in nuclear and mitochondrial DNA, respectively. The two proteins interact to form Atco complexes that serve as the source of Atp9 for ATP synthase assembly. To determine if Atco is also a precursor of COX, we pulse-labeled Cox6 in isolated mitochondria of a cox6 nuclear mutant with COX6 in mitochondrial DNA. Only a small fraction of the newly translated Cox6 was found to be present in Atco, which can explain the low concentration of COX and poor complementation of the cox6 mutation by the allotopic gene. This and other pieces of evidence presented in this study indicate that Atco is an obligatory source of Cox6 for COX biogenesis. Together with our finding that atp9 mutants fail to assemble COX, we propose a regulatory model in which Atco unidirectionally couples the biogenesis of COX to that of the ATP synthase to maintain a proper ratio of these two complexes of oxidative phosphorylation.

DOI: https://doi.org/10.26508/lsa.202301965

Front Cell Neurosci. 2023 ;17 1216487

Neuropathological characterization of the cavitating leukoencephalopathy caused by COA8 cytochrome c oxidase deficiency: a case report.

Alexandra Chapleau, Renée-Myriam Boucher, Tomi Pastinen, Isabelle Thiffault, Peter V Gould, Geneviève Bernard.

COA8-related leukoencephalopathy is a recently described rare cavitating leukoencephalopathy caused by biallelic variants in the COA8 gene. Clinically, it presents heterogeneously and usually follows a bi-phasic clinical course with a period of acute onset and regression, followed by stabilization, and in some cases, even subtle improvement. We present a 4-year-old boy with a homozygous 2.5 kilobase pair deletion in the COA8 gene following a severe neurological deterioration resulting in death weeks after onset. Brain MRI revealed a distinctive pattern of cavitating leukodystrophy predominantly involving the posterior cerebral white matter which improved upon a follow-up MRI a month later. Brain pathology displayed overall white matter destruction with gliosis and infiltration by macrophages. There was preservation of astrocytes around blood vessels and axons around the zones of demyelination. This study is the first neuropathological examination of COA8-related leukoencephalopathy and provides further characterization of the clinical and MRI phenotype.

Keywords: APOPT1; COA8-related leukoencephalopathy; COX deficiency; case report; cavitating leukoencephalopathy; mitochondrial disorders; neuropathology

DOI: https://doi.org/10.3389/fncel.2023.1216487