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)

AAA ATPases form a large protein family with manifold cellular roles. They belong to the AAA+ superfamily of ringshaped P-loop NTPases, which exert their activity through the energy-dependent unfolding of macromolecules. Phylogenetic analyses have suggested the existence of five major clades of AAA domains (proteasome subunits, metalloproteases, domains D1 and D2 of ATPases with two AAA domains, and the MSP1/katanin/spastin group), as well as a number of deeply branching minor clades. These analyses however have been characterized by a lack of consistency in defining the boundaries of the AAA family. We have used cluster analysis to delineate unambiguously the group of AAA sequences within the AAA+ superfamily. Phylogenetic and cluster analysis of this sequence set revealed the existence of a sixth major AAA clade, comprising the mitochondrial, membrane-bound protein BCS1 and its homologues. In addition, we identified several deep branches consisting mainly of hypothetical proteins resulting from genomic projects. Analysis of the AAA N-domains provided direct support for the obtained phylogeny for most branches, but revealed some deep splits that had not been apparent from phylogenetic analysis and some unexpected similarities between distant clades. It also revealed highly degenerate D1 domains in plant MSP1 sequences and in at least one deeply branching group of hypothetical proteins (YC46), showing that AAA proteins with two ATPase domains arose at least three times independently.
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PMID:Phylogenetic analysis of AAA proteins. 1503 33

The beet cyst nematode Heterodera schachtii induces syncytia in the roots of Arabidopsis thaliana, which are its only nutrient source. One gene, At1g64110, that is strongly up-regulated in syncytia as shown by RT-PCR, quantitative RT-PCR, in situ RT-PCR and promoter::GUS lines, encodes an AAA+-type ATPase. Expression of two related genes in syncytia, At4g28000 and At5g52882, was not detected or not different from control root segments. Using amiRNA lines and T-DNA mutants, we show that At1g64110 is important for syncytium and nematode development. At1g64110 was also inducible by wounding, jasmonic acid, salicylic acid, heat and cold, as well as drought, sodium chloride, abscisic acid and mannitol, indicating involvement of this gene in abiotic stress responses. We confirmed this using two T-DNA mutants that were more sensitive to abscisic acid and sodium chloride during seed germination and root growth. These mutants also developed significantly smaller roots in response to abscisic acid and sodium chloride. An in silico analysis showed that ATPase At1g64110 (and also At4g28000 and At5g52882) belong to the 'meiotic clade' of AAA proteins that includes proteins such as Vps4, katanin, spastin and MSP1.
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PMID:An Arabidopsis ATPase gene involved in nematode-induced syncytium development and abiotic stress responses. 2348 Apr 2

Yme1L is an AAA protease that is embedded in the mitochondrial inner membrane with its catalytic domain facing the mitochondrial inner-membrane space. However, how Yme1L regulates mammalian mitochondrial function is still obscure. We find that endogenous Yme1L locates at punctate structures of mitochondria, and that loss of Yme1L in mouse embryonic fibroblast (MEF) cells results in mitochondrial fragmentation and leads to significant increased 'kiss-and-run' type of mitochondrial fusion; however, Yme1L knockdown (shYme1L (short hairpin-mediated RNA interference of Yme1L)) cells still remain normal mitochondrial fusion although shYme1L mitochondria have a little bit less fusion and fission rates, and the shYme1L-induced fragmentation is due to a little bit more mitochondrial fission than fusion in cells. Furthermore, shYme1L-induced mitochondrial fragmentation is independent on optic atrophy 1 (OPA1) S1 or S2 processing, and shYme1L results in the stabilization of OPA1 long form (L-OPA1); in addition, the exogenous expression of OPA1 or L-OPA1 facilitates the shYme1L-induced mitochondrial fragmentation, thus this fragmentation induced by shYme1L appears to be associated with L-OPA1's stability. ShYme1L also causes a slight increase of mitochondrial dynamics proteins of 49 kDa and mitochondrial fission factor (Mff), which recruit mitochondrial key fission factor dynamin-related protein 1 (Drp1) into mitochondria in MEF cells, and loss of Drp1 or Mff inhibits the shYme1L-induced mitochondrial fragmentation. In addition, there is interaction between SLP-2 with Yme1L and shYme1L cells retain stress-induced mitochondrial hyperfusion. Taken together, our results clarify how Yme1L regulates mitochondrial morphology.
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PMID:Loss of Yme1L perturbates mitochondrial dynamics. 2417 54

Mitochondrial protein quality control is crucial for the maintenance of correct mitochondrial homeostasis. It is ensured by several specific mitochondrial proteases located across the various mitochondrial subcompartments. Here, we focused on characterization of functional overlap and cooperativity of proteolytic subunits AFG3L2 (AFG3 Like Matrix AAA Peptidase Subunit 2) and YME1L (YME1 like ATPase) of mitochondrial inner membrane AAA (ATPases Associated with diverse cellular Activities) complexes in the maintenance of mitochondrial structure and respiratory chain integrity. We demonstrate that loss of AFG3L2 and YME1L, both alone and in combination, results in diminished cell proliferation, fragmentation of mitochondrial reticulum, altered cristae morphogenesis, and defective respiratory chain biogenesis. The double AFG3L2/YME1L knockdown cells showed marked upregulation of OPA1 protein forms, with the most prominent increase in short OPA1 (optic atrophy 1). Loss of either protease led to marked elevation in OMA1 (OMA1 zinc metallopeptidase) (60 kDa) and severe reduction in the SPG7 (paraplegin) subunit of the m-AAA complex. Loss of the YME1L subunit led to an increased Drp1 level in mitochondrial fractions. While loss of YME1L impaired biogenesis and function of complex I, knockdown of AFG3L2 mainly affected the assembly and function of complex IV. Our results suggest cooperative and partly redundant functions of AFG3L2 and YME1L in the maintenance of mitochondrial structure and respiratory chain biogenesis and stress the importance of correct proteostasis for mitochondrial integrity.
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PMID:Loss of Mitochondrial AAA Proteases AFG3L2 and YME1L Impairs Mitochondrial Structure and Respiratory Chain Biogenesis. 3054 62

Muscle atrophy is closely associated with many diseases, including diabetes and cardiac failure. Growing evidence has shown that mitochondrial dysfunction is related to muscle atrophy; however, the underlying mechanisms are still unclear. To elucidate how mitochondrial dysfunction causes muscle atrophy, we used hindlimb-immobilized mice. Mitochondrial function is optimized by balancing mitochondrial dynamics, and we observed that this balance shifted towards mitochondrial fission and that MuRF1 and atrogin-1 expression levels were elevated in these mice. We also found that the expression of yeast mitochondrial escape 1-like ATPase (Yme1L), a mitochondrial AAA protease was significantly reduced both in hindlimb-immobilized mice and carbonyl cyanide m-chlorophenylhydrazone (CCCP)-treated C2C12 myotubes. When Yme1L was depleted in myotubes, the short form of optic atrophy 1 (Opa1) accumulated, leading to mitochondrial fragmentation. Moreover, a loss of Yme1L, but not of LonP1, activated AMPK and FoxO3a and concomitantly increased MuRF1 in C2C12 myotubes. Intriguingly, the expression of myostatin, a myokine responsible for muscle protein degradation, was significantly increased by the transient knock-down of Yme1L. Taken together, our results suggest that a deficiency in Yme1L and the consequential imbalance in mitochondrial dynamics result in the activation of FoxO3a and myostatin, which contribute to the pathological state of muscle atrophy.
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PMID:Down-regulation of the mitochondrial i-AAA protease Yme1L induces muscle atrophy via FoxO3a and myostatin activation. 3172 1