The human extended mitochondrial metabolic network: new hubs from lipids.

Even if systems thinking is not new in biology, rationalizing the explosively growing amount of knowledge has been the compelling reason for the sudden rise and spreading of systems biology. Based on 'omics' data, several genome-scale metabolic networks have been reconstructed and validated. One of the most striking aspects of complex metabolic networks is the pervasive power-law appearance of metabolite connectivity. However, the combinatorial diversity of some classes of compounds, such as lipids, has been scarcely considered so far. In this work, a lipid-extended human mitochondrial metabolic network has been built and analyzed. It is shown that, considering combinatorial diversity of lipids and multipurpose enzymes, an intimate connection between membrane lipids and oxidative phosphorilation appears. This finding leads to some biomedical considerations on diseases involving mitochondrial enzymes. Moreover, the lipid-extended network still shows power-law features. Power-law distributions are intrinsic to metabolic network organization and evolution. Hubs in the lipid-extended mitochondrial network strongly suggest that the "RNA world" and the "lipid world" hypothesis are both correct.