Iowa Mutant Apolipoprotein A-I (ApoA-IIowa) ...
Document type :
Article dans une revue scientifique
DOI :
PMID :
Permalink :
Title :
Iowa Mutant Apolipoprotein A-I (ApoA-IIowa) Fibrils Target Lysosomes
Author(s) :
Kameyama, Hirokazu [Auteur]
Tokushima University
Nakajima, Hiroyuki [Auteur]
Tokushima University
Nishitsuji, Kazuchika [Auteur]
Tokushima University
Mikawa, Shiho [Auteur]
Tokushima University
Uchimura, Kenji [Auteur]
Nagoya University
Kobayashi, Norihiro [Auteur]
Kobe University
Okuhira, Keiichiro [Auteur]
Tokushima University
Saito, Hiroyuki [Auteur]
Kyoto University
Sakashita, Naomi [Auteur]
Tokushima University
Tokushima University
Nakajima, Hiroyuki [Auteur]
Tokushima University
Nishitsuji, Kazuchika [Auteur]
Tokushima University
Mikawa, Shiho [Auteur]
Tokushima University
Uchimura, Kenji [Auteur]

Nagoya University
Kobayashi, Norihiro [Auteur]
Kobe University
Okuhira, Keiichiro [Auteur]
Tokushima University
Saito, Hiroyuki [Auteur]
Kyoto University
Sakashita, Naomi [Auteur]
Tokushima University
Journal title :
Scientific Reports
Abbreviated title :
Sci Rep
Volume number :
6
Pages :
30391
Publication date :
2016-07-28
ISSN :
2045-2322
English keyword(s) :
Protein Aggregates
Cell Line
Signal Transduction
Humans
Actins
Dynamins
Lysosomes
Autophagy
Protein Aggregation, Pathological
Mutant Proteins
Mitochondria
Models, Biological
Proteolysis
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
HEK293 Cells
Apolipoprotein A-I
Membrane Potential, Mitochondrial
Hydrogen-Ion Concentration
Cell Line
Signal Transduction
Humans
Actins
Dynamins
Lysosomes
Autophagy
Protein Aggregation, Pathological
Mutant Proteins
Mitochondria
Models, Biological
Proteolysis
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
HEK293 Cells
Apolipoprotein A-I
Membrane Potential, Mitochondrial
Hydrogen-Ion Concentration
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1-83) of apoA-I containing ...
Show more >The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1-83) of apoA-I containing this mutation deposit as amyloid fibrils in patients' tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis.Show less >
Show more >The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1-83) of apoA-I containing this mutation deposit as amyloid fibrils in patients' tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis.Show less >
Language :
Anglais
Audience :
Non spécifiée
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Collections :
Submission date :
2020-02-12T15:11:35Z
2021-03-25T09:53:19Z
2021-03-25T09:53:19Z
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