Premium
Tissue‐specific metabolic regulations of respiration and ROS production of the heart, brain and spinal cord mitochondria
Author(s) -
Panov Alexander,
Dikalov Sergey,
Dambinova Svetlana
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb482
Subject(s) - mitochondrion , oxidative phosphorylation , carnitine , respiration , glutamate receptor , biochemistry , bioenergetics , chemistry , pyruvate dehydrogenase complex , biology , medicine , endocrinology , anatomy , enzyme , receptor
In vivo mitochondria oxidize several metabolites simultaneously. Therefore, changes in metabolic condition associated with age (menopause in women) or disease (diabetes) may have distinct effect on mitochondria from different organs. We tested this hypothesis by analysis of heart (HM), brain (BM) and spinal cord (SCM) mitochondria isolated from young Sprague Dawley rats using Percoll purification step. Pyruvate, glutamate, malate, succinate, palmitoyl‐carnitine and their mixtures were used as substrates. Clark electrode and Amplex Red method were used to measure respiration and ROS generation. HM oxidized palmitoyl‐carnitine or succinate alone very poorly in State 3, and respiration was inhibited upon uncoupling. Combination of palmitoyl‐carnitine with any other mitochondrial substrate increased the rates of oxidative phosphorylation and uncoupled respiration by 40 to 70%, State 4 respiration by 64%, and ROS production increased 3–4 folds. BM and SCM did not oxidize palmitoyl‐carnitine. However, when palmitoyl‐carnitine was mixed with glutamate, pyruvate or succinate, the rates of ROS generation increased 4‐fold as compared with glutamate + malate. Conclusions Rat HM, BM and SCM show distinct substrate preferences for maximal rates of oxidative phosphorylation and ROS production. Thus changes in metabolic conditions or food supplements such as carnitine may affect oxidative stress in a tissue‐specific manner. Research was supported by RFFI grant N 09‐04‐01376.