ATP accelerates respiration of mitochondria from rat lung and suppresses their release of hydrogen peroxide.
Lung mitochondria were isolated by differential centrifugation from pentobarbital-anesthetized male rats. One to three millimolar Mg2+-ATP increased the consumption of oxygen of lung mitochondria oxidizing 10 mM succinate > fourfold (P < 0.01) whereas ATP increased the respiration of liver mitochondria by < 35%. ATP also hyperpolarized partially uncoupled lung mitochondria in the presence of the mitochondria-specific antagonist, oligomycin. However, only 20% of the ATPase activity in the lung mitochondria was blocked by oligomycin compared to a blockade of 91% for liver mitochondria. We investigated the effect of reducing the non-mitochondrial ATPase activity in the lung preparation. A purer suspension of lung mitochondria from a Percoll gradient was inhibited 95% by oligomycin. The volume fraction identified as mitochondria by electron microscopy in this suspension (73.6+/- 3.5%) did not differ from that for liver mitochondria (69.1+/- 4.9%). ATP reduced the mean area of the mitochondrial profiles in this Percoll fraction by 15% (P <0.01) and increased its state 3 respiration with succinate as substrate by 1.5-fold (P < 0.01) with no change in the state 4 respiration measured after carboxyatractyloside. Hence, ATP increased the respiratory control ratio (state 3/state 4, P <0.01). In contrast, state 3 respiration with the complex 1-selective substrates, glutamate and malate, did not change with addition of ATP. The acceleration of respiration by ATP was accompanied by decreased production of H2O2. Thus ATP-dependent processes that increase respiration appear to improve lung mitochondrial function while minimizing the release of reactive oxygen species.
Carlson
Drew E
DE
Program in Trauma and Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA. dcarlson@umm.edu
Pumplin
David W
DW
Ghavam
Sarvin
S
Fiedler
Suzelle M
SM
Chiu
William C
WC
Scalea
Thomas M
TM
D000244:Adenosine Diphosphate / Q000096:biosynthesis*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D000251:Adenosine Triphosphatases