Degradation of functional triose phosphate isomerase protein underlies sugarkill pathology

30Citations
Citations of this article
22Readers
Mendeley users who have this article in their library.

Abstract

Triose phosphate isomerase (TPI) deficiency glycolytic enzymopathy is a progressive neurodegenerative condition that remains poorly understood. The disease is caused exclusively by specific missense mutations affecting the TPI protein and clinically features hemolytic anemia, adult-onset neurological impairment, degeneration, and reduced longevity. TPI has a well-characterized role in glycolysis, catalyzing the isomerization of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3-phosphate (G3P); however, little is known mechanistically about the pathogenesis associated with specific recessive mutations that cause progressive neurodegeneration. Here, we describe key aspects of TPI pathogenesis identified using the TPIsugarkill mutation, a Drosophila model of human TPI deficiency. Specifically, we demonstrate that the mutant protein is expressed, capable of forming a homodimer, and is functional. However, the mutant protein is degraded by the 20S proteasome core leading to loss-of-function pathogenesis. Copyright © 2008 by the Genetics Society of America.

Cite

CITATION STYLE

APA

Seigle, J. L., Celotto, A. M., & Palladino, M. J. (2008). Degradation of functional triose phosphate isomerase protein underlies sugarkill pathology. Genetics, 179(2), 855–862. https://doi.org/10.1534/genetics.108.087551

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free