Type

Journal Article

Authors

J H M Prehn
H J Huber
P Völler
S Kacmar
M Würstle
S Anguissola
C G Concannon
M Rehm
H Düssmann

Subjects

Biochemistry

Topics
luminescent proteins cell membrane permeability male prostatic neoplasms models biological cell line tumor microscopy confocal bcl 2 homologous antagonist killer protein systems biology physiology humans bak1 protein human rna small interfering mitochondrial membranes bax protein human fluorescence resonance energy transfer genetics bcl 2 associated x protein metabolism signal transduction

Single-cell quantification of Bax activation and mathematical modelling suggest pore formation on minimal mitochondrial Bax accumulation. (2009)

Abstract Mitochondrial outer membrane permeabilisation (MOMP) during apoptosis is triggered by the activation and oligomerisation of Bax and Bak, but a quantification of these processes in individual cells has not yet been performed. Single-cell imaging of Bax translocation and oligomerisation in Bax-deficient DU-145 cells expressing CFP-Bax and YFP-Bax revealed that both processes started only minutes before or concomitantly with MOMP, with the majority of Bax translocation and oligomerisation occurring downstream of MOMP. Quantification of YFP-Bax concentrations at mitochondria revealed an increase of only 1.8 + or - 1.5% at MOMP onset. This was increased to 11.2 + or - 3.6% in bak-silenced cells. These data suggested that Bax activation exceeded by far the quantities required for MOMP induction, and that minimal Bax or Bak activation may be sufficient to trigger rapid pore formation. In a cellular automaton modelling approach that incorporated the quantities and movement probabilities of Bax and its inhibitors, activators and enablers in the mitochondrial membrane, we could re-model rapid pore formation kinetics at submaximal Bax activation.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

J H M Prehn, H J Huber, P Völler, S Kacmar, M Würstle, S Anguissola, C G Concannon, M Rehm, H Düssmann

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Heinrich J Huber
Royal College of Surgeons in Ireland
Total Publications: 39
 
3
Maximilian L Würstle
Royal College of Surgeons in Ireland
Total Publications: 13
 
4
Caoimhín G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46
 
5
Markus Rehm
Royal College of Surgeons in Ireland
Total Publications: 55
 
6
Heiko Düssmann
Royal College of Surgeons in Ireland
Total Publications: 45