Mutations in the SPTLC1 protein cause mitochondrial structural abnormalities and endoplasmic reticulum stress in lymphoblasts.

Abstract

Mutations in serine palmitoyltransferase long chain subunit 1 (SPTLC1) cause the typical length-dependent axonal degeneration hereditary sensory neuropathy type 1 (HSN1). Transmission electron microscopy studies on SPTLC1 mutant lymphoblasts derived from patients revealed specific structural abnormalities of mitochondria. Swollen mitochondria with abnormal cristae were clustered around the nucleus, with some mitochondria being wrapped in rough endoplasmic reticulum (ER) membranes. Total mitochondrial counts revealed a significant change in mitochondrial numbers between healthy and diseased lymphocytes but did not reveal any change in length to width ratios nor were there any changes to cellular function. However, there was a notable change in ER homeostasis, as assessed using key ER stress markers, BiP and ERO1-Lα, displaying reduced protein expression. The observations suggest that SPTLC1 mutations cause mitochondrial abnormalities and ER stress in HSN1 cells.

• Authors: Simon J Myers, Chandra S Malladi, Ryan A Hyland, Tara Bautista, Ross Boadle, Phillip J Robinson, Garth A Nicholson
• Journal: DNA and cell biology (DNA Cell Biol) Vol. 33 Issue 7 Pg. 399-407 (Jul 2014) ISSN: 1557-7430 [Electronic] United States
• PMID: 24673574 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SPTLC1 protein, human
• Serine C-Palmitoyltransferase

Topics

• Blotting, Western
• Endoplasmic Reticulum Stress (genetics)
• Flow Cytometry
• Humans
• Lymphocytes (pathology, ultrastructure)
• Microscopy, Confocal
• Mitochondria (chemistry, genetics, ultrastructure)
• Mutation (genetics)
• Serine C-Palmitoyltransferase (genetics)