A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts - PubMed (original) (raw)

Biochemical analysis of respiratory chain function in knockout (filled bars) and control (open bars) mouse hearts at 2 (2w), 4 (4w), and 8 (8w) weeks of age. Bars present mean levels ± SEM. Asterisks indicate level of statistical significance: *, P < 0.05; **, P < 0.01; ***, P < 0.001. (A) Citrate synthase (CS) activity in heart muscle. (B) Relative enzyme activities of respiratory chain enzymes. NADH cytochrome c reductase (NCR), corresponding to complex I + III; NADH coenzyme Q reductase (NQR), complex I; succinate:cytochrome c reductase (SCR), complex II + III; cytochrome c oxidase (COX), complex IV. The relative enzyme activities presented as 100% in the figure correspond to the following absolute ratios of enzyme activity per unit of CS activity at 2, 4, and 8 weeks of age, respectively: NCR, 1.32, 0.74 and 0.75; NQR, 0.35, 0.22, and 0.23; SCR, 0.77, 0.66, and 0.78; COX, 2.88, 2.45, and 2.36. (C) Measurements of MAPR, per unit of CS activity, by using substrates that enter the respiratory chain at different points. The relative MAPR/CS presented as 100% in the figure corresponds to the following absolute ratios of MAPR/unit of CS activity at 2, 4, and 8 weeks of age, respectively: glutamate plus succinate (G + S), 0.27, 0.26, and 0.27; TMPD plus ascorbate (T + A), 0.25, 0.26, and 0.26; palmitoyl-

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-carnitine plus malate (PC + M), 0.22, 0.15, and 0.14; succinate plus rotenone (S + R), 0.05, 0.05 and 0.05. (D) Measurements of MAPR per kg of muscle. The relative MAPR/kg presented as 100% in the figure corresponds to the following absolute ratios of MAPR/kg of heart muscle (mmol/ATP/min/kg heart muscle) at 2, 4, and 8 weeks of age, respectively: G + S, 71, 86, and 97; T + A, 66, 86, and 94; PC + M, 57, 50, and 52; S + R, 13, 17, and 19.