Mitochondrial proteins in hypertrophy and atrophy: a transcript analysis in rat heart.
1. Metabolic processes are acutely and chronically regulated in response to changes in the workload of the heart. Acute changes in cardiac work result in activation and inactivation of existing enzymes and in altered fluxes through existing metabolic pathways. Sustained or chronic changes in cardiac work result in both trophic and transcriptional alterations. 2. The metabolic consequences of a sustained increase or decrease in the workload of the heart are surprisingly uniform and consist of a switch from the predominant oxidation of fatty acids to oxidation of glucose. 3. This switch is reflected in the changes of the transcript levels of three key regulators of mitochondrial function: pyruvate dehydrogenase kinase 4 (PDK4), which phosphorylates and inactivates the pyruvate dehydrogenase complex, malonyl-CoA decarboxylase (MCD), which regulates malonyl-CoA levels and, therefore, rates of beta-oxidation of long-chain fatty acids, and uncoupling protein 3 (UCP-3), which uncouples the oxidative phosphorylation of ADP. 4. The transcript levels of all three proteins are downregulated in hypertrophy as well as in atrophy of rat heart. All three transcripts are transcriptionally regulated by the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). 5. Diminished expression of PPARalpha and PPARalpha-regulated genes constitutes an adaptive mechanism in response to altered workload, because reactivation of PPARalpha in hypertrophied heart results in severe contractile dysfunction.
Taegtmeyer
Heinrich
H
The University of Texas Houston Medical School, Department of Internal Medicine, Division of Cardiology, Houston, Texas 77030, USA. Heinrich.Taegtmeyer@uth.tmc.edu
Razeghi
Peter
P
Young
Martin E
ME
D000818:Animals; D001284:Atrophy; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods*; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D051381:Rats
D024101:Mitochondrial Proteins