RT Journal Article
T1 Genetically Engineered Triple MAPT-Mutant Human-Induced Pluripotent Stem Cells (N279K, P301L, and E10+16 Mutations) Exhibit Impairments in Mitochondrial Bioenergetics and Dynamics.
A1 Szabo, Leonora
A1 Grimm, Amandine
A1 García-León, Juan Antonio
A1 Verfaillie, Catherine M.
A1 Eckert, Anne
K1 Tubulinas
K1 Estrés oxidativo
K1 Mitocondrias
AB Pathological abnormalities in the tau protein give rise to a variety of neurodegenerative diseases, conjointly termed tauopathies. Several tau mutations have been identified in the tau-encoding gene MAPT, affecting either the physical properties of tau or resulting in altered tau splicing. At early disease stages, mitochondrial dysfunction was highlighted with mutant tau compromising almost every aspect of mitochondrial function. Additionally, mitochondria have emerged as fundamental regulators of stem cell function. Here, we show that compared to the isogenic wild-type triple MAPT-mutant human-induced pluripotent stem cells, bearing the pathogenic N279K, P301L, and E10+16 mutations, exhibit deficits in mitochondrial bioenergetics and present altered parameters linked to the metabolic regulation of mitochondria. Moreover, we demonstrate that the triple tau mutations disturb the cellular redox homeostasis and modify the mitochondrial network morphology and distribution. This study provides the first characterization of disease-associated tau-mediated mitochondrial impairments in an advanced human cellular tau pathology model at early disease stages, ranging from mitochondrial bioenergetics to dynamics. Consequently, comprehending better the influence of dysfunctional mitochondria on the development and differentiation of stem cells and their contribution to disease progression may thus assist in the potential prevention and treatment of tau-related neurodegeneration.
PB MDPI
YR 2023
FD 2023-05-13
LK https://hdl.handle.net/10630/27196
UL https://hdl.handle.net/10630/27196
LA eng
NO Szabo L, Grimm A, García-León JA, Verfaillie CM, Eckert A. Genetically Engineered Triple MAPT-Mutant Human-Induced Pluripotent Stem Cells (N279K, P301L, and E10+16 Mutations) Exhibit Impairments in Mitochondrial Bioenergetics and Dynamics. Cells. 2023; 12(10):1385. https://doi.org/10.3390/cells12101385
NO Partial funding for open access charge: Universidad de Málaga
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026