Expression profile analysis of mt protein and mRNA under a dysfunctional mt state Eukaryotic cells can monitor and respond to changes in mt conditions through alterations of nuclear gene expression [32] . To understand how cells respond to the dysfunctional r 0 state to facilitate survival, we analyzed the expression profiles of mt proteins and mRNAs. We found that 40% of mt proteins (274 = 127+147) exhibited a positive correlation between protein and mRNA abundances, while 43% of mt proteins (296 = 78+218) exhibited a negative correlation between protein and mRNA abundances ( Figure 4A ). By using the kmeans clustering algorithm, the mRNA and protein-expression profiles were divided into five groups depending on the abundance ratios of mt protein-mRNA: up-up (127), downdown (147), up-down (78), down-up (218), and unchanged (118) groups ( Figure 4A and Table S4 for protein list). We found that up-regulated and down-regulated functional modules exhibited distinctive patterns in expression profiles ( Figure 4B and C; details in Table S3 ). Specifically, both protein and mRNA abundances increased in the five up-regulated functional modules ( Figure 4B ). Conversely, mRNA abundances increased, but mt protein levels were decreased in the eight down-regulated functional modules ( Figure 4C ). The upregulated functional modules were involved in mtDNA maintenance and control of mt protein transport. The downregulated functional modules were associated with mitochondrial energy production and metabolism. These results suggest that cells actively modulate the expression and transport of mt proteins depending on the functions necessary to survival under pathological conditions.