Parkin is transcriptionally regulated by ATF4: evidence for an interconnection between mitochondrial stress and ER stress

• Published in: Cell death and differentiation Vol. 18; no. 5; pp. 769 - 782
• Main Authors: Bouman, L, Schlierf, A, Lutz, A K, Shan, J, Deinlein, A, Kast, J, Galehdar, Z, Palmisano, V, Patenge, N, Berg, D, Gasser, T, Augustin, R, Trümbach, D, Irrcher, I, Park, D S, Wurst, W, Kilberg, M S, Tatzelt, J, Winklhofer, K F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2011; Nature Publishing Group
• Subjects: 631/208/200; 631/443/319/333; 692/699/375/365/1718; Activating Transcription Factor 4 - metabolism; Apoptosis; Basal ganglia; Base Sequence; Biochemistry; Biomedical and Life Sciences; c-Jun protein; Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology; Cell Biology; Cell Cycle Analysis; Cell Death; Cell Line; Cell survival; Central nervous system diseases; Cyclic AMP response element-binding protein; Disease; eIF-2 Kinase - metabolism; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - physiology; Enzyme Inhibitors - adverse effects; Genes, Reporter; Homeostasis; Humans; Ionophores - pharmacology; Kinases; Life Sciences; Luciferases, Renilla - biosynthesis; Membrane Potential, Mitochondrial; Mitochondria; Mitochondria - drug effects; Mitochondria - physiology; Movement disorders; Mutation; Neurodegeneration; Neurodegenerative diseases; Original Paper; Parkin protein; Parkinson's disease; Pathogenesis; Promoter Regions, Genetic; Promoters; Proteasome Endopeptidase Complex - physiology; proteasomes; Protein folding; Proteins; Proto-Oncogene Proteins c-jun - metabolism; Repressors; Response Elements - genetics; RNA Interference; Signal Transduction; Stem Cells; Stress; Stress, Physiological; Thapsigargin - adverse effects; Transcription factors; Transcription, Genetic; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism; Unfolded Protein Response; Up-Regulation; Germany; ER stress; c-Jun; Parkinson's disease; parkin; UPR; ATF4; mitochondria

Loss of parkin function is responsible for the majority of autosomal recessive parkinsonism. Here, we show that parkin is not only a stress-protective, but also a stress-inducible protein. Both mitochondrial and endoplasmic reticulum (ER) stress induce an increase in parkin-specific mRNA and protein...