title: Translating m-AAA protease function in mitochondria to hereditary spastic paraplegia.
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.
authors.affiliation: Istituto Nazionale Neurologico C. Besta, Division of Biochemistry and Genetics, 20126 Milan, Italy.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Rugarli
authors.forename: Thomas
authors.initials: T
authors.lastname: Langer
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D001369:Axons / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology* / Q000473:pathology; D051336:Mitochondrial Membranes / Q000201:enzymology; D023421:Models, Animal; D009154:Mutation; D010641:Phenotype; D017510:Protein Folding; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015419:Spastic Paraplegia, Hereditary / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: C505819:MrpL32 protein, S cerevisiae; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; C114583:m-AAA proteases; D000074183:ATPases Associated with Diverse Cellular Activities