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キーワード:
ATPases Associated with Diverse Cellular Activities
Adenosine Triphosphatases/genetics/*metabolism
Amino Acid Sequence
Animals
Metalloendopeptidases/chemistry/deficiency/genetics/*metabolism
Mice
Mitochondria/*enzymology
Mitochondrial Membranes/metabolism
Models, Biological
Molecular Sequence Data
Mutation
Protein Biosynthesis
Ribosomal Proteins/metabolism
Ribosomes/*metabolism
Saccharomyces cerevisiae/genetics/growth & development/metabolism
Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
Sequence Homology, Amino Acid
Spastic Paraplegia, Hereditary/*enzymology/genetics
Substrate Specificity
要旨:
AAA proteases comprise a conserved family of membrane bound ATP-dependent proteases that ensures the quality control of mitochondrial inner-membrane proteins. Inactivation of AAA proteases causes pleiotropic phenotypes in various organisms, including respiratory deficiencies, mitochondrial morphology defects, and axonal degeneration in hereditary spastic paraplegia (HSP). The molecular basis of these defects, however, remained unclear. Here, we describe a regulatory role of an AAA protease for mitochondrial protein synthesis in yeast. The mitochondrial ribosomal protein MrpL32 is processed by the m-AAA protease, allowing its association with preassembled ribosomal particles and completion of ribosome assembly in close proximity to the inner membrane. Maturation of MrpL32 and mitochondrial protein synthesis are also impaired in a HSP mouse model lacking the m-AAA protease subunit paraplegin, demonstrating functional conservation. Our findings therefore rationalize mitochondrial defects associated with m-AAA protease mutants in yeast and shed new light on the mechanism of axonal degeneration in HSP.
