Ischemic preconditioning enhances fatty acid-dependent mitochondrial uncoupling.
This study tests the hypothesis that ischemic preconditioning (IP) changes fatty acid (FA)-dependent uncoupling between mitochondrial respiration and oxidative phosphorylation. We found that IP does not alter mitochondrial membrane integrity or FA levels, but enhances membrane potential decreases when FA are present, in an ATP-sensitive manner. FA hydroperoxides had equal effects in control and preconditioned mitochondria, and GTP did not abrogate the IP effect, suggesting uncoupling proteins were not involved. Conversely, thiol reductants and atractyloside, which inhibits the adenine nucleotide translocator, eliminated the differences in responses to FA. Together, our results suggest that IP leads to thiol oxidation and activation of the adenine nucleotide translocator, resulting in enhanced FA transport and mild mitochondrial uncoupling.
Carreira
Raquel S
RS
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, Cidade Universitária, 05508-900 São Paulo, São Paulo, Brazil.
Miyamoto
Sayuri
S
Di Mascio
Paolo
P
Gonçalves
Lino M
LM
Monteiro
Pedro
P
Providência
Luís A
LA
Kowaltowski
Alicia J
AJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration; D005227:Fatty Acids / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008564:Membrane Potentials; D008929:Mitochondria, Heart / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008955:Models, Cardiovascular; D010085:Oxidative Phosphorylation; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071256:Uncoupling Protein 1
D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000071256:Uncoupling Protein 1; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases