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Abstract

Impaired proteolysis and protein folding leading to the accumulation of protein aggregates has been implicated in a series of neurodegenerative disorders. Research in this field has emphasised the important role of protein quality control systems consisting of molecular chaperones, proteases and ancillary factors in disease mechanisms. Mitochondrial dysfunction has recently been linked to neurodegeneration by the identification of disease-causing mutations in components of the highly conserved and ubiquitous organellar quality control system. These include a membrane-bound ATP-dependent AAA protease as well as the mitochondrial chaperonin Hsp60. A functional impairment of either component causes axonal degeneration in hereditary spastic paraplegia (HSP). This review summarises our current knowledge on mitochondrial protein quality control and its implications for the pathogenesis of HSP.