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

Simon J. Myers, Chandra S. Malladi, Ryan A. Hyland, Tara Bautista, Ross Boadle, Phillip J. Robinson, Garth A. Nicholson*

*Corresponding author for this work

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)399-407
Number of pages9
JournalDNA and Cell Biology
Volume33
Issue number7
DOIs
Publication statusPublished - 1 Jul 2014
Externally publishedYes

Fingerprint Dive into the research topics of 'Mutations in the SPTLC1 protein cause mitochondrial structural abnormalities and endoplasmic reticulum stress in lymphoblasts'. Together they form a unique fingerprint.

  • Cite this

    Myers, S. J., Malladi, C. S., Hyland, R. A., Bautista, T., Boadle, R., Robinson, P. J., & Nicholson, G. A. (2014). Mutations in the SPTLC1 protein cause mitochondrial structural abnormalities and endoplasmic reticulum stress in lymphoblasts. DNA and Cell Biology, 33(7), 399-407. https://doi.org/10.1089/dna.2013.2182