Tissue heterogeneity of the mammalian mitochondrial proteome.
The functionality of the mitochondrion is primarily determined by nuclear encoded proteins. The mitochondrial functional requirements of different tissues vary from a significant biosynthetic role (liver) to a primarily energy metabolism-oriented organelle (heart). The purpose of this study was to compare the mitochondrial proteome from four different tissues of the rat, brain, liver, heart, and kidney, to provide insight into the extent of mitochondrial heterogeneity and to further characterize the overall mitochondrial proteome. Mitochondria were isolated, solubilized, digested, and subjected to quantitative liquid chromatography-mass spectroscopy. Of the 16,950 distinct peptides detected, 8,045 proteins were identified. High-confidence identification threshold was reached by 1,162 peptides, which were further analyzed. Of these 1,162 proteins, 1,149 were significantly different in content (P and q values < 0.05) between at least 2 tissues, whereas 13 were not significantly different between any tissues. Confirmation of the mitochondrial origin of proteins was determined from the literature or via NH(2)-terminal mitochondrial localization signals. With these criteria, 382 proteins in the significantly different groups were confirmed to be mitochondrial, and 493 could not be confirmed to be mitochondrial but were not definitively localized elsewhere in the cell. A total of 145 proteins were assigned to the rat mitochondrial proteome for the first time via their NH(2)-terminal mitochondrial localization signals. Among the proteins that were not significantly different between tissues, three were confirmed to be mitochondrial. Most notable of the significantly different proteins were histone family proteins and several structural proteins, including tubulin and intermediate filaments. The mitochondrial proteome from each tissue had very specific characteristics indicative of different functional emphasis. These data confirm the notion that mitochondria are tuned by the nucleus for specific functions in different tissues.
Johnson
D Thor
DT
Laboratory of Cardiac Energetics, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Dr., Rm. B1D416, Bethesda, MD 20892-1061, USA. rsb@nih.gov
Harris
Robert A
RA
French
Stephanie
S
Blair
Paul V
PV
You
Jinsam
J
Bemis
Kerry G
KG
Wang
Mu
M
Balaban
Robert S
RS
D000595:Amino Acid Sequence; D000818:Animals; D002853:Chromatography, Liquid; D006657:Histones / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010085:Oxidative Phosphorylation; D011487:Protein Conformation; D020543:Proteome / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry
D006657:Histones; D020543:Proteome