The cICAT-labeled peptides were loaded on a nanospray tip coupled to a capillary reverse-phase column (14 cm675 mm, Magic C18aq; Michrom BioResources, Auburn, CA) packed inhouse by using a helium pressure cell. Peptides were eluted with a linear gradient of 5-35% buffer B (running buffer A: 0.1% formic acid in H 2 O; elution buffer B: 0.1% formic acid in 100% acetonitrile) over 90 min at 200 nl/min using an Agilent 1100 capillary pump system. Eluting peptides from the column were analyzed using LTQ linear ion trap mass spectrometers (Thermo Finnigan, San Jose, CA). A MS survey scan from 300-2000 m/z was acquired with three mscans followed by three data-dependent MS/MS scans (isolation width, 1.5 m/z; normalized collision energy, 28%; dynamic exclusion lists, 100; dynamic exclusion duration, 3 min). Data from RAW MS/MS files (minimum ion counts, 15; minimum peak intensity threshold, 1; mass range, 600-4300 Da) were generated, and peptide sequences from the data were assigned against the International Protein Index (IPI) human database (Version 3.13; 57,034 proteins) including known contaminants (180 entries) by using a 4-node SEQUEST (version 27, revision 9) cluster with the following search parameters: specificity (no enzyme), number of missed cleavage (max three sites), cysteine mass (fixed, +227.13 for light cICAT), cysteine mass (variable, +9 for heavy cICAT), methionine mass (variable, +16 for oxidation), mass tolerance of precursor ion (3.0) and fragment ion (0.5), mass type of precursor and fragment ion (average mass), and subsequence (cysteine residue). To discriminate true proteins from false positives and to quantify the abundance of proteins, we used Trans-Proteomic Pipeline of Institute for Systems Biology (TPP; Version 1.7.2; INTERACT, PeptideProphet TM , ProteinProphet TM , XPRESS programs). The peptides with P$0.50 by PeptideProphet TM were applied to ProteinProphet TM . The proteins with P$0.95 by ProteinProphet TM were considered to have the correct identification. Single-and double-hit proteins of the correct identifications were further validated through manual inspections of MS/MS spectra (false positive rate, below 0.4%). Quantification of peptides and proteins was performed with XPRESS software, and the peptides with bad quality (e.g., below S/N#2) were not considered by quantification. Finally, we identified nuclear-encoded 1,121 mt proteins that included 313 down-regulated proteins (r 0 /r + #0.67), 201 up-regulated proteins (r 0 /r + $1.5), and 607 not significantly changed (0.67,r 0 / r + ,1.5) proteins. The thresholds of 0.67 represents the 1.5-fold decrease (r 0 /r + #1/1.5), whereas the threshold of 1.5 represents 1.5-fold increase (r 0 /r + $1.5). Protein abundance ratio smaller than 0.67 or larger than 1.5 were routinely-applied thresholds indicating significant changes in proteomic analyses [64, 65, 66, 67] . See Table S1 for further details on the list of identified mt proteins.