Novel p.P298L SURF1 mutation in thiamine deficient Leigh syndrome patients compromises cytochrome c oxidase activity.

Abstract

SURF1 is a nuclear gene and encodes for an important assembly factor for cytochrome c oxidase enzyme. A number of mutations in SURF1 gene render cytochrome c oxidase deficiency, a major causative factor for Leigh syndrome. We screened all the 9 exons and exon-intron boundaries of SURF1 gene in 165 Indian Leigh syndrome patients who were thiamine responsive too. Consequently, we identified several novel and reported nucleotide variations in this gene. The nucleotide changes were analysed by using different in-silico tools for predicting their pathogenicity. Based upon the predictions, we further validated the analyzed functional significance of p.N249D and p.P298L mutations in SURF1 protein using COS-7 cells. Though, both the mutations did not affect the localization of SURF1protein into the mitochondria. But, interestingly the novel mutation p.P298L was reported to significantly compromise the COX activity in these cells.

• Authors: Shalini Mani, G R Chandak, Keshav K Singh, Rajender Singh, S Narasimha Rao
• Journal: Mitochondrion (Mitochondrion) Vol. 53 Pg. 91-98 (07 2020) ISSN: 1872-8278 [Electronic] Netherlands
• PMID: 32380162 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Chemical References

• Membrane Proteins
• Mitochondrial Proteins
• Surf-1 protein
• Electron Transport Complex IV

Topics

• Animals
• COS Cells
• Child
• Chlorocebus aethiops
• Electron Transport Complex IV (metabolism)
• Genetic Predisposition to Disease
• Humans
• India
• Leigh Disease (complications, genetics, metabolism)
• Membrane Proteins (genetics, metabolism)
• Mitochondrial Proteins (genetics, metabolism)
• Polymorphism, Single Nucleotide
• Thiamine Deficiency (genetics, metabolism)