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P1‐076: Number, shape, and distribution of mitochondria in HEK293/Tau cells by 3D‐imaging technique
Author(s) -
Chen Li-Ping,
Wei Yu-Ping,
Tian Qing
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.06.273
Subject(s) - hek 293 cells , mitochondrion , nucleus , cell , microbiology and biotechnology , microtubule , cell culture , biology , chemistry , biochemistry , genetics
Background:Abnormal mitochondrial dynamics and distribution as well as autophagy impairment are well characterized in brain of Alzheimer’s patient. Moreover, previous works have demonstrated mitochondrial failure in these patients’ fibroblasts leading us to wonder if mitochondrial recycling might be affected. Methods: Mitochondrial function and recycling has been studied in human skin fibroblasts and brain biopsies from sporadic Alzheimer disease patients. PARK2 overexpression by a lentiviral vector has been used to improve mitophagy in fibroblasts. Results: Fibroblasts showed slower mitochondrial membrane potential recovery together with alterations in lysosomes and autophagy, accompanied by an increase of oxidized and ubiquitinated proteins. Impairment in mitophagy has been proven due to diminished PARK2 and insufficient vesicle induction, accumulating depolarized mitochondria and PINK1. The augmented D1 PINK1 fragment levels shown suggest an inhibitory effect over PARK2 translocation and activation. These features have been also found in brain samples. Moreover, the enhancement of PARK2 was able to reverse the described pathology. Conclusions: Our findings indicate that mitophagy alterations can be considered a new hallmark of sporadic Alzheimer disease. Mitophagy study in peripheral tissue might be used with diagnosis porpoises. How these alterations correlate with different stages of the disease should be studied. The therapeutic potential of PARK2 highlights a common link between sporadic and familial forms and with other neuropathies such as Parkinson. Further efforts should be done to improve autophagy as a therapeutic strategy.