title: Mitochondrial proteins in neuronal degeneration.
abstract: In this review, we highlight recent findings about the role of some mitochondrial proteins in neurological diseases. Studies in mice gene-deleted for Omi/HtrA2 and AIF showed the involvement of these mitochondrial proteins in selective cell degeneration in the spinal cord and brain. In humans, mutations in the mitochondrial protein, Paraplegin, cause an autosomal form of hereditary spastic paraplegia with an enhanced sensitivity to oxidative stress. Reactive oxygen species and decreased respiratory chain activity in mitochondria also contribute to common neurological diseases. The mitochondrial uncoupling protein, Ucp-2, was found to be neuroprotective in experimental stroke and brain trauma. Recent proteomic and profiling studies have revealed the existence of additional mitochondrial proteins with unknown functions. The elucidation of the physiological functions of mitochondrial proteins may lead to new insights into the role of these organelles in cell degeneration and to identification of novel drug targets for the prevention and treatment of different diseases.
authors.affiliation: Department of Neuroscience, Uppsala University, Biomedical Centre, Box 587, S-751 23 Uppsala, Sweden. Dan.Lindholm@helsinki.fi
authors.forename: Dan
authors.initials: D
authors.lastname: Lindholm
authors.forename: Ove
authors.initials: O
authors.lastname: Eriksson
authors.forename: Laura
authors.initials: L
authors.lastname: Korhonen
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009410:Nerve Degeneration / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; C494830:AIFM1 protein, mouse; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2; C000615915:Htra2 protein, mouse; D008666:Metalloendopeptidases; C112889:SPG7 protein, human; C491813:Spg7 protein, mouse; D000074183:ATPases Associated with Diverse Cellular Activities