RT Journal Article
T1 Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts.
A1 Lofaro, Francesco-Demetrio
A1 Boraldi, Federica
A1 García-Fernández, María Inmaculada
A1 Lara, Estrella
A1 Valdivielso-Felices, Pedro
A1 Quaglino, Daniela
K1 Fibroblastos
K1 Tejido conjuntivo - Enfermedades - Tratamiento
AB PXE is a genetic disease considered as a paradigm of ectopic mineralization disorders, being characterized by multisystem clinical manifestations due to progressive calcification of skin, eyes, and the cardiovascular system, resembling an age-related phenotype. Although fibroblasts do not express the pathogenic ABCC6 gene, nevertheless these cells are still under investigation because they regulate connective tissue homeostasis, generating the "arena" where cells and extracellular matrix components can promote pathologic calcification and where activation of pro-osteogenic factors can be associated to pathways involving mitochondrial metabolism. The aim of the present study was to integrate structural and bioenergenetic features to deeply investigate mitochondria from control and from PXE fibroblasts cultured in standard conditions and to explore the role of mitochondria in the development of the PXE fibroblasts' pathologic phenotype. Proteomic, biochemical, and morphological data provide new evidence that in basal culture conditions (1) the protein profile of PXE mitochondria reveals a number of differentially expressed proteins, suggesting changes in redox balance, oxidative phosphorylation, and calcium homeostasis in addition to modified structure and organization, (2) measure of oxygen consumption indicates that the PXE mitochondria have a low ability to cope with a sudden increased need for ATP via oxidative phosphorylation, (3) mitochondrial membranes are highly polarized in PXE fibroblasts, and this condition contributes to increased reactive oxygen species levels, (4) ultrastructural alterations in PXE mitochondria are associated with functional changes, and (5) PXE fibroblasts exhibit a more abundant, branched, and interconnected mitochondrial network compared to control cells, indicating that fusion prevail over fission events. In summary, the present study demonstrates that mitochondria are modified in PXE fibroblasts.
PB Frontiers Media
YR 2020
FD 2020-12-17
LK https://hdl.handle.net/10630/35341
UL https://hdl.handle.net/10630/35341
LA eng
NO Lofaro FD, Boraldi F, Garcia-Fernandez M, Estrella L, Valdivielso P and Quaglino D (2020) Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts. Front. Cell Dev. Biol. 8:610266. doi: 10.3389/fcell.2020.610266
NO This study was supported by a grant from PXE Italia Onlus E96C18000600007. FDL mobility was supported by the UnimoreInternational Mobility grant A.006@MOBAT_3@03BS.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026