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Mutations affecting mitochondrial function are among the most common forms of inborn errors of metabolism, primarily affecting infants and children. When such mitochondrial dysfunction leads to cardiac involvement, termed the mitochondrial cardiomyopathies, mortality rates increase threefold. In studying animal and cell models of these diseases, we have found that mitochondrial calcium levels are increased and are currently investigating (a) how such regulation occurs, and (b) how such changes affect cardiac function.