129966 20241125101135.0 doi 10.1016/j.freeradbiomed.2023.12.006 sideral 136221 ART-2023-136221 eng Gaudó, Paula ATAD3C regulates ATAD3A assembly and function in the mitochondrial membrane 2023 Access copy available to the general public Unrestricted Mitochondrial ATAD3A is an ATPase Associated with diverse cellular Activities (AAA) domain containing enzyme, involved in the structural organization of the inner mitochondrial membrane and of increasing importance in childhood disease. In humans, two ATAD3A paralogs arose by gene duplication during evolution: ATAD3B and ATAD3C. Here we investigate the cellular activities of the ATAD3C paralog that has been considered a pseudogene. We detected unique ATAD3C peptides in HEK 293T cells, with expression similar to that in human tissues, and showed that it is an integral membrane protein that exposes its carboxy-terminus to the intermembrane space. Overexpression of ATAD3C, but not of ATAD3A, in fibroblasts caused a decrease in cell proliferation and oxygen consumption rate, and an increase of cellular ROS. This was due to the incorporation of ATAD3C monomers in ATAD3A complex in the mitochondrial membrane reducing its size. Consistent with a negative regulation of ATAD3A function in mitochondrial membrane organization, ATAD3C expression led to increased accumulation of respiratory chain dimeric CIII in the inner membrane, to the detriment to that assembled in respiratory supercomplexes. Our results demonstrate a negative dominant role of the ATAD3C paralog with implications for mitochondrial OXPHOS function and suggest that its expression regulates ATAD3A in the cell. info:eu-repo/grantAgreement/ES/ISCIII-EDRF/PT17-0019 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 7.1 2023 ENDOCRINOLOGY & METABOLISM 15 / 186 = 0.081 2023 Q1 T1 BIOCHEMISTRY & MOLECULAR BIOLOGY 35 / 313 = 0.112 2023 Q1 T1 1.752 2023 Physiology (medical) 2023 Q1 Biochemistry 2023 Q1 14.0 2023 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion de Tomás-Mateo, Elena Garrido-Pérez, Nuria Universidad de Zaragoza (orcid)0000-0003-0145-3020 Santana, Alfredo Ruiz-Pesini, Eduardo Universidad de Zaragoza (orcid)0000-0002-0269-7337 Montoya, Julio Universidad de Zaragoza (orcid)0000-0003-1770-6299 Bayona-Bafaluy, Pilar Universidad de Zaragoza (orcid)0000-0002-8585-6371 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 211 (2023), 114-126 Free radic. biol. med. FREE RADICAL BIOLOGY AND MEDICINE 0891-5849 6378689 http://zaguan.unizar.es/record/129966/files/texto_completo.pdf Versión publicada 2466720 http://zaguan.unizar.es/record/129966/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:129966 articulos driver 2024-11-22-12:00:36 ARTICLE