title: Mitochondrial protein alterations in a familial peripheral neuropathy caused by the V144D amino acid mutation in the sphingolipid protein, SPTLC1.
abstract: Axonal degeneration is the final common path in many neurological disorders. Subsets of neuropathies involving the sensory neuron are known as hereditary sensory neuropathies (HSNs). Hereditary sensory neuropathy type I (HSN-I) is the most common subtype of HSN with autosomal dominant inheritance. It is characterized by the progressive degeneration of the dorsal root ganglion (DRG) with clinical symptom onset between the second or third decade of life. Heterozygous mutations in the serine palmitoyltransferase (SPT) long chain subunit 1 (SPTLC1) gene were identified as the pathogenic cause of HSN-I. Ultrastructural analysis of mitochondria from HSN-I patient cells has displayed unique morphological abnormalities that are clustered to the perinucleus where they are wrapped by the endoplasmic reticulum (ER). This investigation defines a small subset of proteins with major alterations in abundance in mitochondria harvested from HSN-I mutant SPTLC1 cells. Using mitochondrial protein isolates from control and patient lymphoblasts, and a combination of 2D gel electrophoresis, immunoblotting and mass spectrometry, we have shown the increased abundance of ubiquinol-cytochrome c reductase core protein 1, an electron transport chain protein, as well as the immunoglobulin, Ig kappa chain C. The regulation of these proteins may provide a new route to understanding the cellular and molecular mechanisms underlying HSN-I.
authors.affiliation: Neuro-Cell Biology Laboratory, University of Western Sydney, Penrith, Australia ; Molecular Medicine Research Group, University of Western Sydney, Penrith, Australia ; School of Science and Health, University of Western Sydney, Penrith, Australia.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Stimpson
authors.affiliation: Molecular Physiology, University of Western Sydney, Penrith, Australia ; Molecular Medicine Research Group, University of Western Sydney, Penrith, Australia ; School of Science and Health, University of Western Sydney, Penrith, Australia ; School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751 Australia ; School of Medicine, University of Western Sydney, Office 30.2.15, Campbelltown campus, Locked Bag 1797, Penrith, NSW 2751 Australia.
authors.forename: Jens R
authors.initials: JR
authors.lastname: Coorssen
authors.affiliation: Neuro-Cell Biology Laboratory, University of Western Sydney, Penrith, Australia ; Molecular Medicine Research Group, University of Western Sydney, Penrith, Australia ; School of Science and Health, University of Western Sydney, Penrith, Australia ; School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751 Australia ; University of Western Sydney, Office 21.1.05, Campbelltown campus, Locked Bag 1797, Penrith, NSW 2751 Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Myers
keywords: Hereditary sensory neuropathy type 1; Mitochondria; Serine palmitoyltransferase long chain subunit 1; Ubiquinol-cytochrome c reductase core protein 1