• Something wrong with this record ?

Two components in pathogenic mechanism of mitochondrial ATPase deficiency: energy deprivation and ROS production

Tomáš Mráček, Petr Pecina, Alena Vojtíšková, Martin Kalous, Ondrej Šebesta, Josef Houštěk

. 2006 ; 41 (7) : 683-6877.

Language English Country Great Britain

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

Persistent link   https://www.medvik.cz/link/bmc13027430

Grant support
NR7790 MZ0 CEP Register

Isolated defects of mitochondrial ATPase due to diminished biosynthesis of the enzyme represent new class of severe mitochondrial diseases of nuclear origin. The primary cause of decreased cellular content of ATPase appears to be a problem in assembly of the F1 catalytic part of the enzyme. With the aim to elucidate how the low ATPase content affects mitochondrial energy provision and ROS production, we have investigated fibroblasts from patients with ATPase decrease to 10-30%. Measurements of cellular respiration showed pronounced decrease in ATPase capacity for basal respiration, mitochondrial ATP synthesis was decreased to 26-33%. Cytofluorometric analysis using TMRM revealed altered discharge of mitochondrial membrane potential (DeltaPsim) in patient cells, which was 20 mV increased at state 3-ADP. Analysis of ROS production by CM-H2DCFDA demonstrated 2-fold increase in ROS production in patient cells compared to controls. ROS production rate was sensitive to uncoupler (FCCP) and thus apparently related to increased DeltaPsim. Our studies clearly demonstrate that low ATPase content and decreased mitochondrial ATP production lead to high values of DeltaPsim and are associated with activation of ROS generation by the mitochondrial respiratory chain. In conclusion, both the energetic deprivation and increased oxidative stress are important components of the pathogenic mechanism of ATPase disorders.

References provided by Crossref.org

Bibliography, etc.

Literatura

000      
00000naa a2200000 a 4500
001      
bmc13027430
003      
CZ-PrNML
005      
20130902141911.0
007      
ta
008      
130822s2006 xxkd f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.exger.2006.02.009 $2 doi
035    __
$a (PubMed)16581217
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Mráček, Tomáš $7 xx0122128 $u Department of Bioenergetics, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4-Krc, Czech Republic.
245    10
$a Two components in pathogenic mechanism of mitochondrial ATPase deficiency: energy deprivation and ROS production / $c Tomáš Mráček, Petr Pecina, Alena Vojtíšková, Martin Kalous, Ondrej Šebesta, Josef Houštěk
504    __
$a Literatura
520    9_
$a Isolated defects of mitochondrial ATPase due to diminished biosynthesis of the enzyme represent new class of severe mitochondrial diseases of nuclear origin. The primary cause of decreased cellular content of ATPase appears to be a problem in assembly of the F1 catalytic part of the enzyme. With the aim to elucidate how the low ATPase content affects mitochondrial energy provision and ROS production, we have investigated fibroblasts from patients with ATPase decrease to 10-30%. Measurements of cellular respiration showed pronounced decrease in ATPase capacity for basal respiration, mitochondrial ATP synthesis was decreased to 26-33%. Cytofluorometric analysis using TMRM revealed altered discharge of mitochondrial membrane potential (DeltaPsim) in patient cells, which was 20 mV increased at state 3-ADP. Analysis of ROS production by CM-H2DCFDA demonstrated 2-fold increase in ROS production in patient cells compared to controls. ROS production rate was sensitive to uncoupler (FCCP) and thus apparently related to increased DeltaPsim. Our studies clearly demonstrate that low ATPase content and decreased mitochondrial ATP production lead to high values of DeltaPsim and are associated with activation of ROS generation by the mitochondrial respiratory chain. In conclusion, both the energetic deprivation and increased oxidative stress are important components of the pathogenic mechanism of ATPase disorders.
590    __
$a bohemika - dle Pubmed
650    12
$a adenosintrifosfatasy $x nedostatek $7 D000251
650    02
$a adenosintrifosfát $x biosyntéza $7 D000255
650    02
$a kultivované buňky $7 D002478
650    12
$a energetický metabolismus $7 D004734
650    02
$a lidé $7 D006801
650    02
$a membránové potenciály $7 D008564
650    12
$a mitochondrie $x metabolismus $7 D008928
650    12
$a reaktivní formy kyslíku $x metabolismus $7 D017382
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Pecina, Petr $7 xx0141218
700    1_
$a Vojtíšková, Alena $7 _AN035246
700    1_
$a Kalous, Martin, $d 1957- $7 mzk2004258360
700    1_
$a Šebesta, Ondřej $7 xx0215134
700    1_
$a Houštěk, Josef, $7 xx0030591 $d 1947-
773    0_
$t Experimental Gerontology $x 0531-5565 $g Roč. 41, č. 7 (2006), s. 683-6877 $p Exp Gerontol $w MED00001745
773    0_
$p Exp Gerontol $g 41(7):683-7, 2006 Jul $x 0531-5565
910    __
$a ABA008 $b A 3795 $y 3 $z 0
990    __
$a 20130822135730 $b ABA008
991    __
$a 20130902142358 $b ABA008
999    __
$a ok $b bmc $g 991389 $s 825858
BAS    __
$a 3
BMC    __
$x MED00001745 $i 0531-5565 $a 2006 $b 41 $c 7 $d 683-6877 $m Experimental gerontology $n Exp Gerontol
GRA    __
$a NR7790 $p MZ0
LZP    __
$a 2013-08/gvbo

Find record

Citation metrics

Archiving options