An Efficient Lentiviral-based Proteomics Approach Identifies Mitochondrial Complexes with Neurodegenerative Function

Abstract

Perturbations in proteins involved in the mitochondrial processes have emerged as a causative factor in a wide range of life-threatening human diseases, such as neurodegenerative disorders. In fact, mitochondrial dysfunctions are argued to be the first step in triggering the onset of other deleterious events that collectively act causally in the pathogenesis of diseases. Accordingly, dysfunctions in mitochondrial proteins influence the proper functioning of basic processes, such as energy metabolism and reactive species production. Indeed, biochemical and genetic evidence has provided molecular insights into the role of mitochondrial proteins and complexes in isolation, yet our understanding of how mitochondrial proteins cause and/or contribute to the diverse array of human diseases, including neurodegeneration remains unclear. Like any other biological system, mitochondria are linked together by extensive networks of physical (protein-protein) interactions; therefore a detailed understanding of the systems properties is required to unravel their role in neurodegenerative diseases. To address this, I have developed and optimized an effective procedure to identify the physically interacting proteins for generating a mitochondrial protein-protein interaction network for those involved in various neurodegenerative diseases.