We separated the mitochondrial protein functional network into functional modules ( Figure 1A) . A functional module was determined by examining whether a group of proteins was physically connected or functionally linked. To identify modules, we used hierarchical average-linkage clustering by using the OC software (http://www.compbio.dundee.ac.uk/Software/OC/oc. html) with the STRING confidence scores as a similarity measure. STRING confidence score represented the probability of finding the proteins which were related by one or more cellular and genetic interactions. Then, we assigned biological function to the module by using Ontologizer 2.0, which collects GO representative functional annotations from proteins in each module [63] , and selected functional modules if the significance (p-value) of GO enrichment was less than 0.01. The enrichment of up-or downregulated proteins in a given functional module was used to check the consistency of protein expression in the module (hypergeometric tests, p-value ,0.01). Finally, we identified 13 functional modules consisting of five up-regulated and eight down-regulated modules.