Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two membrane-bound ATP-dependent AAA proteases conduct protein quality surveillance in the inner membrane of mitochondria and control crucial steps during mitochondrial biogenesis. AAA domains of proteolytic subunits are critical for the recognition of non-native membrane proteins which are extracted from the membrane bilayer for proteolysis. Here, we have analysed the role of the conserved loop motif YVG, which has been localized to the central pore in other hexameric AAA(+) ring complexes, for the degradation of membrane proteins by the i-AAA protease Yme1. Proteolytic activity was found to depend on the presence of hydrophobic amino acid residues at position 354 within the pore loop of Yme1. Mutations affected proteolysis in a substrate-specific manner: whereas the degradation of misfolded membrane proteins was impaired at a post-binding step, folded substrate proteins did not interact with mutant Yme1. This reflects most likely deficiencies in the ATP-dependent unfolding of substrate proteins, since we observed similar effects for ATPase-deficient Yme1 mutants. Our findings therefore suggest an essential function of the central pore loop for the ATP-dependent translocation of membrane proteins into a proteolytic cavity formed by AAA proteases.
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PMID:Substrate specific consequences of central pore mutations in the i-AAA protease Yme1 on substrate engagement. 1652 90

OPA1, a dynamin-related guanosine triphosphatase mutated in dominant optic atrophy, is required for the fusion of mitochondria. Proteolytic cleavage by the mitochondrial processing peptidase generates long isoforms from eight messenger RNA (mRNA) splice forms, whereas further cleavages at protease sites S1 and S2 generate short forms. Using OPA1-null cells, we developed a cellular system to study how individual OPA1 splice forms function in mitochondrial fusion. Only mRNA splice forms that generate a long isoform in addition to one or more short isoforms support substantial mitochondrial fusion activity. On their own, long and short OPA1 isoforms have little activity, but, when coexpressed, they functionally complement each other. Loss of mitochondrial membrane potential destabilizes the long isoforms and enhances the cleavage of OPA1 at S1 but not S2. Cleavage at S2 is regulated by the i-AAA protease Yme1L. Our results suggest that mammalian cells have multiple pathways to control mitochondrial fusion through regulation of the spectrum of OPA1 isoforms.
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PMID:OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. 1770 29

Tim54p, a component of the inner membrane TIM22 complex, does not directly mediate the import of inner membrane substrates but is required for assembly/stability of the 300-kD TIM22 complex. In addition, Deltatim54 yeast exhibit a petite-negative phenotype (also observed in yeast harboring mutations in the F1Fo ATPase, the ADP/ATP carrier, mitochondrial morphology components, or the i-AAA protease, Yme1p). Interestingly, other import mutants in our strain background are not petite-negative. We report that Tim54p is not involved in maintenance of mitochondrial DNA or mitochondrial morphology. Rather, Tim54p mediates assembly of an active Yme1p complex, after Yme1p is imported via the TIM23 pathway. Defective Yme1p assembly is likely the major contributing factor for the petite-negativity in strains lacking functional Tim54p. Thus, Tim54p has two independent functions: scaffolding/stability for the TIM22 membrane complex and assembly of Yme1p into a proteolytically active complex. As such, Tim54p links protein import, assembly, and turnover pathways in the mitochondrion.
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PMID:Tim54p connects inner membrane assembly and proteolytic pathways in the mitochondrion. 1789 42