hide
Free keywords:
ATP-Dependent Proteases
Adenosine Triphosphatases/genetics/*metabolism
Adenosine Triphosphate/*physiology
Binding Sites
Electron Transport Complex IV/metabolism
Fungal Proteins/genetics/*metabolism
Intracellular Membranes/*metabolism
Membrane Proteins/*metabolism
*Metalloendopeptidases
Mitochondria/*metabolism/ultrastructure
Mitochondrial Proteins
Mutagenesis, Site-Directed
Recombinant Fusion Proteins/metabolism
Saccharomyces cerevisiae/genetics/*metabolism
*Saccharomyces cerevisiae Proteins
Tetrahydrofolate Dehydrogenase/metabolism
Abstract:
The mechanism of selective protein degradation of membrane proteins in mitochondria has been studied employing a model protein that is subject to rapid proteolysis within the inner membrane. Protein degradation was mediated by two different proteases: (i) the m-AAA protease, a protease complex consisting of multiple copies of the ATP-dependent metallopeptidases Yta1Op (Afg3p) and Yta12p (Rcalp); and (ii) by Ymelp (Ytallp) that also is embedded in the inner membrane. Ymelp, highly homologous to Yta1Op and Yta12p, forms a complex of approximately 850 kDa in the inner membrane and exerts ATP-dependent metallopeptidase activity. While the m-AAA protease exposes catalytic sites to the mitochondrial matrix, Ymelp is active in the intermembrane space. The Ymelp complex was therefore termed 'i-AAA protease'. Analysis of the proteolytic fragments indicated cleavage of the model polypeptide at the inner and outer membrane surface and within the membrane-spanning domain. Thus, two AAA proteases with their catalytic sites on opposite membrane surfaces constitute a novel proteolytic system for the degradation of membrane proteins in mitochondria.
