Research : Basic Research

Molecular Bioenergetics

The Molecular Bioenergetics laboratories in the Department of Neurology have two main goals: First, to understand the biogenesis of human mitochondria and its regulation and how these processes influence human neuromuscular and neurodegenerative disorders. Second, we are interested in understanding the molecular pathogenesis of mutations in mitochondrial DNA and nDNA that impact mitochondrial function. We are also actively pursuing novel approaches to therapy. These mutations have been associated with devastating clinical syndromes like seizures, strokes, muscle weakness, diabetes and others. For this purposes we use mammalian cell culture, yeast and genetically modified mouse models.

To learn more about the Molecular Biogenetics Laboratories, please see the specific areas of interest below:

Mitochondrial Biogenesis in Health and Disease

Antoni Barrientos, Ph.D., is Associate Professor in the Department of Neurology. His main research interest concerns the biogenesis of mitochondrial membrane complexes involved in biological energy transduction, specifically the components of the mitochondrial respiratory chain and oxidative phosphorylation system. His group works towards understanding how mitochondrial biogenesis is regulated and how it impacts on cellular bioenergetics in health and in human neuromuscular and neurodegenerative disorders. To achieve these goals they are using the facultative anaerobe yeast Saccharomyces cerevisiae as a model organism. Additionally, our projects involve the use of human cultured cells to validate and/or complement the discoveries made in yeast. To learn more please go to our Website Barrientos Lab

Mitochondrial Respiration in Neurological and Degenerative Diseases

Carlos Moraes, Ph.D., is Professor in the Department of Neurology. His group works on the human mtDNA, which is a compact circular genome (16.6 kb) coding for components of the ATP-producing oxidative phosphorylation system. The contribution of the mitochondrial genome to cellular respiration, though vital, is not sufficient. Dozens of nuclear DNA (nDNA) coded proteins synthesized in the cytoplasm are imported into mitochondria and assembled with mitochondrially-synthesized proteins to form a functional oxidative phosphorylation system. Mutations of either mtDNA or nDNA have been associated with devastating clinical syndromes. Organs with high energy requirements such as brain and muscle are preferentially affected. Symptoms include: seizures, strokes, muscle weakness, blindness, diabetes, and hearing loss. In addition to defining novel mtDNA abnormalities in patients with mitochondrial disorders, we are interested in understanding the molecular pathogenesis of these mutations and developing novel approaches to therapy. We use a full array of molecular and cell biology techniques for these studies.

Dr. Moraes is currently funded by four major NIH grants: 1) Development of genetic therapies for mitochondrial diseases. We are focusing on altering the ratio of mutant/wild-type mtDNA by the use of mitochondria-targeted endonucleases; 2) Development of animal models to study the pathogenesis of mitochondrial disorders. We are studying the molecular pathogenesis of several mitochondrial disorders with the help of genetically engineered mouse models; 3) The role of cytochrome c in apoptosis and development. WE have developed genetically modified mice with a defect in cytochrome c in various tissues. We are using this model to study the role of cytochrome c in apoptosis; and 4) Compensating for a defect in oxidative phosphorylation by increasing mitochondrial biogenesis. We have found that the transcription coactivator PGC-1alpha, a major regulator of mitochondrial biogenesis, can compensate for partial mitochondrial defects when overexpressed.