COX is the terminal oxidase of the respiratory chain. COX deficiency is the major cause of mitochondrial encephalomyopathies in humans. Our long-term goal is to attain a complete understanding of the pathways leading to COX assembly and their components as a prerequisite to the development of therapies for the management of disorders associated with COX deficiencies.
Metabolic and mitochondrial abnormalities are a prominent feature of aging and neurodegeneration. However, the literature reports conflicting results concerning the extent and causality of the aging associated aerobic energy production decline and mitochondrial ROS-induced damage, as well as their interplay with nutritional cues. Single cell models have provided key information concerning mechanisms of aging and neurodegeneration.
Over the last few years we have become very interested in the biogenesis of the mitochondrial ribosomes. The process is complicated by the fact that the two mitoribosomal RNAs (rRNAs) are universally mitochondrion-encoded whereas all ribosomal proteins (with a single exception in yeast) are encoded in the nuclear DNA. Its biomedical importance is highlighted by the fact that mutations affecting genes encoding mitochondrial ribosomal subunits are responsible for infantile multisystemic mitochondrial diseases, frequently involving encephalomyopathy and hypertrophic cardiomyopathy.
The mitochondrial respiratory chain (MRC) assembly and function involve the organization of its constitutive complexes in supercomplexes or respirasomes. It is believed that supercomplexes have an important functional role in cellular bioenergetics by optimizing electron transfer, proton pumping and controlling the formation of reactive intermediates. We are investigating the players and mechanisms involved in MRC supercomplex assembly using yeast and cultured human cells as research models.
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