Autophagic degradation of nuclear components in mammalian cells.
Autophagy is an evolutionarily conserved intracellular mechanism for the degradation of organelles and proteins. Here we demonstrate the presence of perinuclear autophagosomes/autolysosomes containing nuclear components in nuclear envelopathies caused by mutations in the genes encoding A-type lamins (LMNA) and emerin (EMD). These autophagosomes/autolysosomes were sometimes bigger than a nucleus. The autophagic nature is further supported by upregulation of LC3-II in Lmna(H222P/H222P) fibroblasts. In addition, inhibition of autophagy led to the accumulation of nuclear abnormalities and reduced cell viability, strongly suggesting a beneficial role of autophagy, at least in these cells. Similar giant autophagosomes/autolysosomes were seen even in wild-type cells, albeit rarely, implying that this "nucleophagy" is not confined to the diseased condition, but may be seen even in physiologic conditions to clean up nuclear wastes produced by nuclear damage.
Park
Young-Eun
YE
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Hayashi
Yukiko K
YK
Bonne
Gisèle
G
Arimura
Takuro
T
Noguchi
Satoru
S
Nonaka
Ikuya
I
Nishino
Ichizo
I
D000818:Animals; D001343:Autophagy; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002470:Cell Survival; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D050505:Mutant Proteins / Q000378:metabolism; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D009685:Nuclear Envelope / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D053140:Organelle Shape; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012867:Skin / Q000473:pathology; D014158:Transcription, Genetic; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
D034904:Lamin Type A; D052119:Lysosomal-Associated Membrane Protein 2; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins