Spatial distribution of cellular function: the partitioning of proteins between mitochondria and the nucleus in MCF7 breast cancer cells.
Concurrent proteomics analysis of the nuclei and mitochondria of MCF7 breast cancer cells identified 985 proteins (40% of all detected proteins) present in both organelles. Numerous proteins from all five complexes involved in oxidative phosphorylation (e.g., NDUFA5, NDUFB10, NDUFS1, NDUF2, SDHA, UQRB, UQRC2, UQCRH, COX5A, COX5B, MT-CO2, ATP5A1, ATP5B, ATP5H, etc.), from the TCA-cycle (DLST, IDH2, IDH3A, OGDH, SUCLAG2, etc.), and from glycolysis (ALDOA, ENO1, FBP1, GPI, PGK1, TALDO1, etc.) were distributed to both the nucleus and mitochondria. In contrast, proteins involved in nuclear/mitochondrial RNA processing/translation and Ras/Rab signaling showed different partitioning patterns. The identity of the OxPhos, TCA-cycle, and glycolysis proteins distributed to both the nucleus and mitochondria provides evidence for spatio-functional integration of these processes over the two different subcellular organelles. We suggest that there are unrecognized aspects of functional coordination between the nucleus and mitochondria, that integration of core functional processes via wide subcellular distribution of constituent proteins is a common characteristic of cells, and that subcellular spatial integration of function may be a vital aspect of cancer.
Proteomics and Molecular Cell Dynamics, Division of Medicine, School of Life and Medical Sciences, University College London, Royal Free Campus, Rowland Hill Street NW3 2PF, United Kingdom.
Amal T
AT
Qattan
Marko
M
Radulovic
Mark
M
Crawford
Jasminka
J
Godovac-Zimmermann
D000595:Amino Acid Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002952:Citric Acid Cycle; D003600:Cytosol / Q000378:metabolism; D030562:Databases, Protein; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006019:Glycolysis; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D058977:Molecular Sequence Annotation; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D020033:Protein Isoforms / Q000032:analysis; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D015203:Reproducibility of Results; D015398:Signal Transduction
D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D020543:Proteome