Autophagic degradation of nuclear components in mammalian cells

Young-Eun Park; Yukiko K Hayashi; Gisèle Bonne; Takuro Arimura; Satoru Noguchi; Ikuya Nonaka; Ichizo Nishino

doi:10.4161/auto.8901

Autophagic degradation of nuclear components in mammalian cells

Autophagy. 2009 Aug;5(6):795-804. doi: 10.4161/auto.8901. Epub 2009 Aug 30.

Authors

Young-Eun Park¹, Yukiko K Hayashi, Gisèle Bonne, Takuro Arimura, Satoru Noguchi, Ikuya Nonaka, Ichizo Nishino

Affiliation

¹ Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.

PMID: 19550147
DOI: 10.4161/auto.8901

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy*
Cell Nucleus / metabolism*
Cell Nucleus / ultrastructure
Cell Survival
Cells, Cultured
Embryo, Mammalian / cytology
Fibroblasts / metabolism*
Fibroblasts / ultrastructure
Green Fluorescent Proteins / metabolism
Humans
Lamin Type A / metabolism
Lysosomal-Associated Membrane Protein 2 / metabolism
Mice
Microtubule-Associated Proteins / metabolism
Muscle, Skeletal / pathology
Muscle, Skeletal / ultrastructure
Mutant Proteins / metabolism
Myocardium / pathology
Myocardium / ultrastructure
Nuclear Envelope / metabolism
Nuclear Envelope / pathology
Nuclear Envelope / ultrastructure
Organelle Shape
Phagosomes / metabolism
Phagosomes / ultrastructure
Recombinant Fusion Proteins / metabolism
Skin / pathology
Transcription, Genetic
Vacuoles / metabolism
Vacuoles / ultrastructure

Substances

Lamin Type A
Lysosomal-Associated Membrane Protein 2
Map1lc3b protein, mouse
Microtubule-Associated Proteins
Mutant Proteins
Recombinant Fusion Proteins
Green Fluorescent Proteins