Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To date, direct analysis of mitochondrial proteomes has largely been limited to animals, fungi and plants. To broaden our knowledge of mitochondrial structure and function, and to provide additional insight into the evolution of this key eukaryotic organelle, we have undertaken the first comprehensive analysis of the mitochondrial proteome of a protist. Highly purified mitochondria from Tetrahymena thermophila, a ciliated protozoon, were digested exhaustively with trypsin and the resulting peptides subjected to tandem liquid chromatography-tandem mass spectrometry (LC/LC-MS/MS). In this way, we directly identified a total of 573 mitochondrial proteins, 545 of which are encoded by the nuclear genome and 28 by the mitochondrial genome. The latter number includes a novel, 44 residue protein (which we designate Ymf78) that had not been recognized during annotation of the T. thermophila mtDNA sequence. The corresponding gene, ymf78, is highly conserved in genomic position, size and sequence within the genus Tetrahymena. Our analysis has provided broad coverage of both membrane-bound and soluble proteins from the various submitochondrial compartments, with prominent representatives including components of the tricarboxylic acid cycle, Complexes I-IV of the electron transport chain and Complex V (ATP synthase), the mitochondrial transcription and translation machinery, the TOM and TIM protein translocases, various mitochondrial transporters, chaperonins (Cpn60, Hsp70, Hsp90), at least four FtsH family ATP-dependent metalloproteases implicated in m-AAA and i-AAA protease function, and enzymes involved in lipid, amino acid and coenzyme metabolism, as well as iron-sulfur cluster formation. Unexpectedly, six of the ten enzymes of glycolysis were found by MS analysis of purified T. thermophila mitochondria, whereas no hits were seen to any cytosolic ribosomal proteins. At least one of the glycolytic proteins, enolase, has an evident N-terminal extension that exhibits characteristics of a typical mitochondrial targeting peptide. As in other organisms, phylogenetic analysis of functionally annotated mitochondrial proteins demonstrates that <20% can be traced confidently to the alpha-proteobacterial lineage of Bacteria, emphasizing the chimeric evolutionary nature of the mitochondrial proteome. Notably, about 45% of the proteins identified in our analysis have no known function, and most of these do not have obvious homologs outside of the ciliate lineage. About two-thirds of these ORFan proteins have putative homologs in another ciliate, Paramecium tetraurelia, whereas the remainder appear to be Tetrahymena-specific. These results emphasize the power and importance of direct MS-based analysis of mitochondria in revealing novel mitochondrial proteins in different eukaryotic lineages. Our observations reinforce an emerging view of the mitochondrion as an evolutionarily flexible organelle, with novel proteins (and presumably functions) being added in a lineage-specific fashion to an ancient, highly conserved functional core, much of which was contributed by the presumptive alpha-proteobacterial symbiont from which the mitochondrial genome was derived.
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PMID:Exploring the mitochondrial proteome of the ciliate protozoon Tetrahymena thermophila: direct analysis by tandem mass spectrometry. 1795 97

Mitochondrial quality control refers to the coordinated cellular systems involved in maintaining a population of healthy mitochondria. In addition to mitochondrial protein chaperones (Hsp10, Hsp60, and others) and proteases (Lon, AAA proteases) needed for refolding or degrading individual proteins, mitochondrial integrity is maintained through the regulation of protein import via the TOM/TIM complex and protein redistribution across the network via fusion and fission and through mitophagy and biogenesis, key determinants of mitochondrial turnover. A growing number of studies point to the importance of mitochondrial dynamics (fusion/fission) and mitochondrial autophagy in the heart. Mitochondrial biogenesis must keep pace with mitophagy in order to maintain a stable number of mitochondria. In this review, we will discuss the use of MitoTimer as a tool to monitor mitochondrial turnover.
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PMID:MitoTimer: a novel protein for monitoring mitochondrial turnover in the heart. 2547 61

Mitochondria have relatively independent protein quality control systems, including their own chaperones for protein folding and AAA proteases for protein degradation. Accumulating evidence has shown that cytosolic proteins and disease-causing misfolded proteins can be translocated into mitochondria and then impinge upon their function. It is important to understand the interplay between cellular proteostasis and mitochondria, as impaired proteostasis and mitochondrial dysfunction are causally linked with aging and age-related disorders. This review highlights our recent finding showing that the outer mitochondrial membrane protein FUNDC1, a previously reported mitophagy receptor, interacts with the chaperone protein HSC70 to mediate the mitochondrial translocation of cytosolic proteasomal substrates via the TOM/TIM complex into the mitochondrial matrix where they can be degraded by LONP1 protease. Excessive accumulation of unfolded proteins within mitochondria triggers the formation of Mitochondrion-Associated Protein Aggregates (MAPAs), which are subsequently autophagically degraded in a FUNDC1-dependent manner. We suggest that mitochondria actively organize the cellular proteostatic response and that the interaction between FUNDC1 and HSC70 may represent a new link between impaired proteostasis, mitochondrial dysfunction and cellular aging.
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PMID:Mitochondria organize the cellular proteostatic response and promote cellular senescence. 3059 55