PMID- 22402226
OWN - NLM
STAT- MEDLINE
DCOM- 20130503
LR  - 20220129
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1817
IP  - 10
DP  - 2012 Oct
TI  - Induction of the permeability transition pore in cells depleted of mitochondrial 
      DNA.
PG  - 1860-6
LID - 10.1016/j.bbabio.2012.02.022 [doi]
AB  - Respiratory complexes are believed to play a role in the function of the 
      mitochondrial permeability transition pore (PTP), whose dysregulation affects the 
      process of cell death and is involved in a variety of diseases, including cancer 
      and degenerative disorders. We investigated here the PTP in cells devoid of 
      mitochondrial DNA (rho(0) cells), which lack respiration and constitute a model for 
      the analysis of mitochondrial involvement in several pathological conditions. We 
      observed that mitochondria of rho(0) cells maintain a membrane potential and that 
      this is readily dissipated after displacement of hexokinase (HK) II from the 
      mitochondrial surface by treatment with either the drug clotrimazole or with a 
      cell-permeant HK II peptide, or by placing rho(0) cells in a medium without serum 
      and glucose. The PTP inhibitor cyclosporin A (CsA) could decrease the 
      mitochondrial depolarization induced by either HK II displacement or by nutrient 
      depletion. We also found that a fraction of the kinases ERK1/2 and GSK3alpha/beta is 
      located in the mitochondrial matrix of rho(0) cells, and that glucose and serum 
      deprivation caused concomitant ERK1/2 inhibition and GSK3alpha/beta activation with the 
      ensuing phosphorylation of cyclophilin D, the mitochondrial target of CsA. 
      GSK3alpha/beta inhibition with indirubin-3'-oxime decreased PTP-induced cell death in 
      rho(0) cells following nutrient ablation. These findings indicate that rho(0) cells 
      are equipped with a functioning PTP, whose regulatory mechanisms are similar to 
      those observed in cancer cells, and suggest that escape from PTP opening is a 
      survival factor in this model of mitochondrial diseases. This article is part of 
      a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012).
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Masgras, Ionica
AU  - Masgras I
AD  - University of Padova, Padova, Italy.
FAU - Rasola, Andrea
AU  - Rasola A
FAU - Bernardi, Paolo
AU  - Bernardi P
LA  - eng
GR  - GGP11082/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120228
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Permeability Transition Pore)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.24 (MAPK1 protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cyclosporine/pharmacology
MH  - DNA, Mitochondrial/genetics/*metabolism
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Glycogen Synthase Kinase 3/genetics/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Hexokinase/genetics/metabolism
MH  - Humans
MH  - Membrane Potential, Mitochondrial/genetics
MH  - Mitochondrial Diseases/genetics/metabolism
MH  - Mitochondrial Membrane Transport Proteins/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Mitochondrial Permeability Transition Pore
MH  - Mitogen-Activated Protein Kinase 1/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/genetics/metabolism
EDAT- 2012/03/10 06:00
MHDA- 2013/05/04 06:00
CRDT- 2012/03/10 06:00
PHST- 2012/01/20 00:00 [received]
PHST- 2012/02/16 00:00 [revised]
PHST- 2012/02/21 00:00 [accepted]
PHST- 2012/03/10 06:00 [entrez]
PHST- 2012/03/10 06:00 [pubmed]
PHST- 2013/05/04 06:00 [medline]
AID - S0005-2728(12)00058-8 [pii]
AID - 10.1016/j.bbabio.2012.02.022 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2012 Oct;1817(10):1860-6. doi: 
      10.1016/j.bbabio.2012.02.022. Epub 2012 Feb 28.