RT info:eu-repo/semantics/article
T1 Impact of compound heterozygous SDHA variants on mitochondrial function in pediatric with neurological disease
A1 Garrido Moraga, Rocío
A1 Serrano Lorenzo, Pablo
A1 Esteban Amo, María J.
A1 Bellusci, Marcello
A1 Fuente García, Miguel Ángel de la
A1 Arenas, Joaquín
A1 González Quintana, Adrián
A1 Ugalde, Cristina
A1 Simarro Grande, María
A1 Martín Casanueva, Miguel Ángel
K1 SDHA gene
K1 Compound heterozygous mutations
K1 Mitochondrial dysfunction
K1 Neurological disorders
K1 3201.02 Genética Clínica
AB This study examines two rare compound heterozygous missense variants in the SDHA gene, c.1535G > A (p.R512Q) and c.1753C > T (p.R585W), identified in a pediatric patient presenting with neurological manifesta-tions, including epilepsy, developmental delay, and optic atrophy. The SDHA gene encodes a key component ofsuccinate dehydrogenase (SDH), an essential enzyme complex at the intersection of two fundamental metabolicpathways: the Krebs cycle, and the mitochondrial respiratory chain (MRC).Patient-derived fibroblasts were used to evaluate the impact of the mutations on SDH activity and MRC as-sembly and function. The analysis revealed significant decreases in SDH activity and subunit levels, as well asimpaired assembly. Additionally, complex I (CI) activity and CI-containing supercomplexes formation were alsoimpaired, indicating more widespread mitochondrial dysfunction. Unexpectedly, basal and maximal respirationrates remained unchanged, though spare respiratory capacity was significantly reduced. These findingsdemonstrate the deleterious effects of the c.1535G > A and c.1753C > T variants, which had previously beenassociated with primary mitochondrial disorder (PMD) and tumors but had not been functionally validated untilnow
PB Elsevier
SN 1567-7249
YR 2026
FD 2026
LK https://uvadoc.uva.es/handle/10324/83787
UL https://uvadoc.uva.es/handle/10324/83787
LA eng
NO Mitochondrion, 2026, vol. 89, p. 102149
NO Producción Científica
DS UVaDOC
RD 25-mar-2026