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Free keywords:
ATPases Associated with Diverse Cellular Activities
Animals
Axons/*enzymology/pathology
Humans
Metalloendopeptidases/genetics/*metabolism
Mice
Mice, Knockout
Mitochondria/*enzymology/pathology
Mitochondrial Membranes/enzymology
Models, Animal
Mutation
Phenotype
Protein Folding
Ribosomal Proteins/genetics/*metabolism
Saccharomyces cerevisiae Proteins/genetics/*metabolism
Spastic Paraplegia, Hereditary/*enzymology/genetics/pathology
Abstract:
Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurodegenerative disorder that is characterized by progressive and cell-specific axonal degeneration. An autosomal recessive form of the disease is caused by mutations in paraplegin, which is a conserved subunit of the ubiquitous and ATP-dependent m-AAA protease in mitochondria. The m-AAA protease carries out protein quality control in the inner membrane of the mitochondria, suggesting a pathogenic role of misfolded proteins in HSP. A recent study demonstrates that the m-AAA protease regulates ribosome assembly and translation within mitochondria by controlling proteolytic maturation of a ribosomal subunit. Here, we will discuss implications of the dual role of the m-AAA protease in protein activation and degradation for mitochondrial dysfunction and axonal degeneration.
