TY  - JOUR
A1  - Schmidt, B.
A1  - Wachter, E.
A1  - Sebald, Walter
A1  - Neupert, W.
T1  - Processing peptidase of Neurospora mitochondria. Two-step cleavage of imported ATPase subunit 9
N2  - Subunit 9 (dicyclohexylcarbodümide binding protein, 'proteolipid') of the mitochondrial F 1F0-ATPase is a nuclearly coded protein in Neurospora crassa. lt is synthesized on free cytoplasmic ribosomes as a larger precursor with an NH2-terminal peptide extension. The peptide extension is cleaved ofT after transport of the protein into the mitochondria. A processing activity referred to as processing peptidase that cleaves the precursor to subunit 9 and other mitochondrial proteins is described and characterized using a cell-free system. Precursor synthesized in vitro was incubated with extracts of mitochondria. Processing peptidase required Mn2 + for its activity. Localization studies suggested that it is a soluble component of the mitochondrial matrix. The precursor was cleaved in two sequential steps via an intermediate-sized polypeptide. The intermediate form in the processing of subunit 9 was also seen in vivo and upon import of the precursor into isolated mitochondria in vitro. The two dcavage sites in the precursor molecule were determined. The data indicate that: {a) the correct NH2-terminus of the mature protein was generated, (b) the NH2-terminal amino acid of the intermediate-sized polypeptide is isoleueine in position -31. The cleavage sites show similarity ofprimary structure. It is concluded that processing peptidase removes the peptide extension from the precursor to subunit 9 (and probably other precursors) after translocation of these polypeptides (or the NHrterminal part of these polypeptides) into the matrix space of mitochondria.
KW  - Biochemie
Y1  - 1984
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62674
ER  - 
TY  - JOUR
A1  - Ziegler, C.
A1  - Richter, J.
A1  - Mahr, M.
A1  - Gajewska, A.
A1  - Schiele, M.A.
A1  - Gehrmann, A.
A1  - Schmidt, B.
A1  - Lesch, K.-P.
A1  - Lang, T.
A1  - Helbig-Lang, S.
A1  - Pauli, P.
A1  - Kircher, T.
A1  - Reif, A.
A1  - Rief, W.
A1  - Vossbeck-Elsebusch, A.N.
A1  - Arolt, V.
A1  - Wittchen, H.-U.
A1  - Hamm, A.O.
A1  - Deckert, J.
A1  - Domschke, K.
T1  - MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy
JF  - Translational Psychiatry
N2  - Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0-T1: +3.37±2.17%), while non-responders further decreased in methylation (-2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02-0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.
KW  - Adult
KW  - Case-Control Studies
KW  - Cognitive Therapy
KW  - DNA Methylation
KW  - Epigenesis
KW  - Genetic
KW  - Female
KW  - Humans
KW  - Monoamine Oxidase/genetics
KW  - Panic Disorder/genetics
KW  - Panic Disorder/therapy
KW  - Sequence Analysis
KW  - DNA
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164422
IS  - 6
ER  -