Human fibroblasts from sporadic Alzheimer's disease (AD) patients show mitochondrial alterations and lysosome dysfunction
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Human fibroblasts from sporadic Alzheimer's disease (AD) patients show mitochondrial alterations and lysosome dysfunction. / Li, Yuan; Li, Zhiquan; Grillo, Emanuela; Desler, Claus; Navarro, Claudia; Bohr, Vilhelm A.; Berliocchi, Laura; Rasmussen, Lene Juel.
In: Free Radical Biology and Medicine, Vol. 222, 2024, p. 569-578.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Human fibroblasts from sporadic Alzheimer's disease (AD) patients show mitochondrial alterations and lysosome dysfunction
AU - Li, Yuan
AU - Li, Zhiquan
AU - Grillo, Emanuela
AU - Desler, Claus
AU - Navarro, Claudia
AU - Bohr, Vilhelm A.
AU - Berliocchi, Laura
AU - Rasmussen, Lene Juel
N1 - Publisher Copyright: © 2024
PY - 2024
Y1 - 2024
N2 - Mitophagy is a mechanism that maintains mitochondrial integrity and homeostasis and is thought to promote longevity and reduce the risk of age-related neurodegenerative diseases, including Alzheimer's disease (AD). Here, we investigate the abundance of mitochondrial reactive oxygen species (ROS), mitochondrial function, and mitophagy in primary fibroblasts from patients with sporadic AD (sAD) and normal healthy controls. The results show increased levels of mitochondrial ROS, changes in mitochondrial morphology, altered bioenergetic properties, and defects in autophagy, mitophagy, and lysosome-mediated degradation pathways in sAD fibroblasts relative to control fibroblasts. Interestingly, lysosome abundance and the staining of lysosomal markers remained high, while the capacity of lysosome-dependent degradation was lower in sAD fibroblasts than in controls fibroblasts. Nicotinamide riboside supplementation decreased mitochondrial ROS, while capacity for lysosomal degradation remained unchanged in sAD fibroblasts relative to healthy control fibroblasts. These findings provide insight into molecular mechanisms involving the dysregulation of lysosome and autophagy/mitophagy pathways that may contribute significantly to clinical signs and pathological features of sAD.
AB - Mitophagy is a mechanism that maintains mitochondrial integrity and homeostasis and is thought to promote longevity and reduce the risk of age-related neurodegenerative diseases, including Alzheimer's disease (AD). Here, we investigate the abundance of mitochondrial reactive oxygen species (ROS), mitochondrial function, and mitophagy in primary fibroblasts from patients with sporadic AD (sAD) and normal healthy controls. The results show increased levels of mitochondrial ROS, changes in mitochondrial morphology, altered bioenergetic properties, and defects in autophagy, mitophagy, and lysosome-mediated degradation pathways in sAD fibroblasts relative to control fibroblasts. Interestingly, lysosome abundance and the staining of lysosomal markers remained high, while the capacity of lysosome-dependent degradation was lower in sAD fibroblasts than in controls fibroblasts. Nicotinamide riboside supplementation decreased mitochondrial ROS, while capacity for lysosomal degradation remained unchanged in sAD fibroblasts relative to healthy control fibroblasts. These findings provide insight into molecular mechanisms involving the dysregulation of lysosome and autophagy/mitophagy pathways that may contribute significantly to clinical signs and pathological features of sAD.
KW - Alzheimer's disease
KW - Autophagy
KW - Lysosome
KW - Mitochondria
KW - Mitophagy
KW - Oxidative stress
U2 - 10.1016/j.freeradbiomed.2024.07.013
DO - 10.1016/j.freeradbiomed.2024.07.013
M3 - Journal article
C2 - 39009245
AN - SCOPUS:85198573897
VL - 222
SP - 569
EP - 578
JO - Free Radical Biology & Medicine
JF - Free Radical Biology & Medicine
SN - 0891-5849
ER -
ID: 399169194