The adenine nucleotide translocator: regulation and function during myocardial development and hypertrophy.
1. The present review focuses on the adenine nucleotide translocator (ANT), which facilitates exchange of cytosolic ADP for mitochondrial ATP. This protein serves a central role in regulating cellular oxidative capacity. 2. The ANT, a nuclear-encoded mitochondrial protein, is developmentally regulated and, thus, accumulates within the mitochondrial membrane during maturation. 3. Accumulation of ANT parallels changes in kinetics of myocardial respiration determined from 31P magnetic resonance spectroscopy studies. 4. Thyroid hormone modulates developmental transitions in ANT content, as well as respiratory control patterns. These transitions are linked to quantitative ANT changes, not to alterations in functionality at individual exchanger sites. 5. Developmental programming for ANT and parallel alterations in oxidative phosphorylation kinetics are relevant to the heart, which exhibits remodelling in response to pathological processes. Maladaptive hearts exhibiting ANT deficits demonstrate ADP-dependent respiratory kinetics similar to the newborn heart. Thus, ANT deficits and alterations in mitochondrial respiratory function may contribute to the pathogenesis of myocardial remodelling and heart failure.
Portman
Michael A
MA
Division of Cardiology, Department of Pediatrics, University of Washington School of Medicine and Children's Hospital and Medical Center, Seattle, Washington, USA. mportm@chmc.org
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D006321:Heart / Q000196:embryology* / Q000254:growth & development / Q000502:physiology; D006801:Humans; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020257:Ventricular Remodeling / Q000502:physiology*
D000226:Mitochondrial ADP, ATP Translocases