bims-cytox1 2026-05-24 papers

Neuromuscul Disord. 2026 May 05. pii: S0960-8966(26)00110-0. [Epub ahead of print]64 106442

A COA8 homozygous mutation presenting as an intermediate CMT with leukopathy.

A Dupic, T Evangelista, B Labella, P Gaignard, P H Becker, H Turmel, M Konyukh, M Masingue.

Patients with cytochrome c oxidase (COX) deficiency exhibit clinical heterogeneity, with onset ranging from infancy to adulthood. COA8-related disorders typically present in childhood with acute symptoms and cavitating posterior leukoencephalopathy, though milder, muscle-predominant forms have recently been reported. We describe a 54-year-old woman with a neuropathy with slow conduction velocities and leukoencephalopathy, associated with hearing loss and migraine. Neurological examination showed mildly high-arched feet, mild dysmetria without lateralization, and distal hypoesthesia. There was no gastro-intestinal involvement. Targeted NGS for hereditary neuropathies was unremarkable. The neurometabolic workup was negative. Whole genome sequencing identified a homozygous COA8 mutation (c.476 + 1G > A), confirmed by muscle biopsy showing COX deficiency and significantly reduced complex IV activity. This case expands the phenotypic spectrum of COA8-related diseases and suggests that a mitochondrial etiology should be considered in cases of neuropathy with intermediate conduction velocities associated with leukoencephalopathy, even with late onset.

Keywords: COA8; COX deficiency; Leukoencephalopathy; Mitochondrial diseases; Sensory-motor neuropathy

DOI: https://doi.org/10.1016/j.nmd.2026.106442

Res Sq. 2026 May 05. pii: rs.3.rs-9589283. [Epub ahead of print]

TACO1 regulates mitochondrial adaptation in hypertension-induced cardiac remodeling and heart failure.

Mitochondrial dysfunction drives hypertensive heart failure and reflects impaired oxidative phosphorylation and altered organelle structure. The mechanisms linking hypertensive signaling to mitochondrial translation and architecture remain unclear. TACO1 is a mitochondrial translational activator required for cytochrome c oxidase subunit I synthesis and may regulate respiratory chain assembly. We tested whether angiotensin II type 1 receptor activation disrupts TACO1-dependent translation and drives inner membrane remodeling. Using mRen also known as (mRen2)27 hypertensive rat hearts, we assessed mitochondrial function, ultrastructure, and metabolism. AT1R activation reduced TACO1-dependent COX I translation and produced a selective deficiency in complex IV activity. This impaired oxidative phosphorylation and increased the production of reactive oxygen species. Mitochondria exhibited reduced volume, increased fragmentation, and disrupted cristae organization with lower integrity scores. Hypertensive hearts also showed reduced expression of OPA1 and MICOS components. Metabolomic profiling separated control and heart failure groups and revealed enrichment of amino acid, nucleotide, and mitochondrial energy pathways. Lipidomic analysis identified coordinated changes across lipid classes consistent with altered membrane composition. Pharmacological AT1R inhibition restored COX I translation, rescued complex IV activity, and improved cristae structure. These findings establish a mechanistic link between hypertensive signaling, mitochondrial translation, cristae organization, and metabolic remodeling in heart failure.

DOI: https://doi.org/10.21203/rs.3.rs-9589283/v1

Comp Biochem Physiol A Mol Integr Physiol. 2026 May 15. pii: S1095-6433(26)00055-3. [Epub ahead of print] 112020

Lack of repeatability in red muscle mitochondrial function over time and across oxygen conditions in a teleost fish.

Jean-Baptiste Quéméneur, José-Luis Zambonino-Infante, Karine Salin.

Mitochondrial aerobic metabolism varies among individuals and has been linked to components of animal performance and fitness. However, because assessments of mitochondrial function have often required terminal sampling, most studies rely on single measurements, leaving the temporal and environmental consistency of mitochondrial traits within individuals largely unknown. Here, we investigated the repeatability of mitochondrial function measurements over time and across environmental conditions using repeated measurements in permeabilized red muscle of individual European sea bass (Dicentrarchus labrax). Mitochondrial metabolic traits were measured at monthly intervals under stable normoxic conditions and following exposure to hypoxia. At the population level, mean mitochondrial function was largely stable over time, with the exception of an increase in cytochrome c oxidase activity under hypoxia. However, mitochondrial respiratory rates, ATP production, and efficiency showed no repeatability within individuals over a one-month period across either stable or changing oxygen conditions. These results indicate that, although individuals differ markedly in mitochondrial function at any given time, mitochondrial phenotypes permeabilized red muscle are highly dynamic and context-dependent. Our findings highlight important limitations in the interpretation of single time-point measurements of mitochondrial metabolism and have implications for studies linking mitochondrial function to performance, ecological responses, and fitness.

Keywords: Biopsy; Individual variation; Red muscle; Sea bass; Temporal repeatability

DOI: https://doi.org/10.1016/j.cbpa.2026.112020