Rational design of organelle compartments in cells

Abstract

Motivation and Objectives
In recent years there is a growing interest in researching on mitochondria, chloroplasts and other mitochondrion-like organelles (e.g. hydrogenosomes, mitosomes and apicoplasts) because of the integrate bio-search for comorbidities- related genes, pathway dysfunctions, the energy balance in aging, inflammation and disease, and the discovery of novel factors involved in organelle division, movement, signaling and adaptation to varying environmental and pathogenic conditions. Furthermore, there is an impressive amount of mitochondria and chloroplasts sequence data (thousands of mitochondrial sequences from many species have been sequenced) that have been used in the last ten years to derive the history of species. Notably, there are no examples of examined eukaryotes without a mitochondrion- related organelle (Shiflett and Johnson, 2010). Despite these research efforts, there is a lack of knowledge about the relationships between the organelles in a cell and its metabolism. We aim at investigating and comparing the complexity of these organelles through a common framework that includes single- and multi-objective optimization, robustness analysis and sensitivity analysis. The possibility of multiobjective- optimization in organelles such as the mitochondrion may be related to the different tasks of maximizing the ATP or the heat, or intermediate compounds of the Krebs cycle in order to provide input for biosynthetic pathways (e.g. the amino acids synthesis). Furthermore, rather than focusing only on networks of molecules, we think of the cell as an integrated system (Yoneda et al, 2009). Indeed, the systems biology approach, i.e. taking into account only molecular networks, misses the analysis of the organization provided by organelles. An organelle can be viewed as a functional organization of macromolecules working to accomplish essential cellular functions. Many conditions depend on a variety of environmental and other factors, and therefore cannot be fully investigated by conventional molecular-level approaches