Flavia Fontanesi, PhD

I am interested in elucidating the molecular mechanisms governing mitochondrial function and biogenesis. Mitochondria play a pivotal role in the conversion of nutrients-derived energy in form of ATP molecules, through the mitochondria-housed pathways of Krebs cycle, beta-oxidation, respiration and oxidative phosphorylation (OXPHOS). The overarching long-term goal of my research is to gain a complete understanding of the biogenesis and function of the mitochondrial OXPHOS system. The understanding of the pathways shaping the mitochondrial respiratory chain remains a central and basic issue in the field of mitochondrial biogenesis and bioenergetics and unquestionably one that carries profound biomedical implications. Indeed, perturbations of mitochondrial metabolism have been linked to diabetes and diabetic complications, including diabetic nephropathy. Currently, I am participating in a study aiming to dissect the role of mitochondrial dysfunction in podocyte injury associated with defect in the cholesterol transporter ABCA1.
My interest in cellular respiratory metabolism started early during my undergraduate and graduate studies, where I characterized the mitochondrial dysfunction associated with ophthalmoplegia. After obtaining my Ph.D. I moved to the University of Miami, where I initially focused my work on the assembly process of cytochrome c oxidase, the last enzyme of the mitochondrial respiratory chain, in yeast and mammalian cell cultures. Furthermore, in the last 10 years, I have extensively worked on the characterization of the factors and molecular mechanisms involved in the regulation of mitochondrial gene expression. This process is essential to mitochondrial biogenesis and function because mitochondria are organelles of endosymbiotic origin, which conserve their own genome and gene expression machinery.
Moreover, I am especially interested in the molecular mechanisms interconnecting the assembly of the different components of the OXPHOS system and in particular the pathways involved in mitochondrial supercomplex biogenesis. Mitochondrial respiratory supercomplexes are macrostructures formed by the dynamic association of two or more individual respiratory complexes. Their functional significance has gain particular attention in the last few years due to increasing evidence of the pivotal role these structures play in cellular fitness in health and disease.